PanelApp (staging)

Activity

Filter

Cancel
Date Panel Item Activity
169 actions
Spontaneous coronary artery dissection v0.56 COL4A1 Zornitza Stark Marked gene: COL4A1 as ready
Spontaneous coronary artery dissection v0.56 COL4A1 Zornitza Stark Gene: col4a1 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.56 COL4A1 Zornitza Stark Phenotypes for gene: COL4A1 were changed from CORONARY ARTERY DISSECTION, SPONTANEOUS MIM#122455 to Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, MIM#611773
Spontaneous coronary artery dissection v0.55 COL4A1 Zornitza Stark Classified gene: COL4A1 as Green List (high evidence)
Spontaneous coronary artery dissection v0.55 COL4A1 Zornitza Stark Gene: col4a1 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.54 COL4A1 Zornitza Stark reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, MIM#611773; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Spontaneous coronary artery dissection v0.54 COL4A1 Stephanie Hesselson gene: COL4A1 was added
gene: COL4A1 was added to Spontaneous coronary artery dissection. Sources: Other
Mode of inheritance for gene: COL4A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A1 were set to PMID: 35583931, 35234813, 37248441
Phenotypes for gene: COL4A1 were set to CORONARY ARTERY DISSECTION, SPONTANEOUS MIM#122455
Penetrance for gene: COL4A1 were set to unknown
Review for gene: COL4A1 was set to GREEN
Added comment: It is possible that rare and common variants in COL4A1 contribute to SCAD risk.

5 individuals with SCAD have been found to carry a LP variant:

PMID: 35234813 reports 3x SCAD participants with a LP variant in COL4A1 p.Gly1484Arg, p.Gly495Arg, and p.Gly160Asp

PMID 35583931 reports 2x SCAD participants with LP variants in COL4A1 p.Gly1198Arg and p.Ala1626Gly

In a meta-GWAS for SCAD, the COL4A1/COL4A2 locus accounted for the second largest proportion of heritability for SCAD in the dataset. It contained two independent GWAS signals at this locus. (PMID 37248441)
Sources: Other
Spontaneous coronary artery dissection v0.54 COL3A1 Zornitza Stark Publications for gene: COL3A1 were set to 30071989
Spontaneous coronary artery dissection v0.53 PKD1 Stephanie Hesselson reviewed gene: PKD1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 29650765,33125268,26971055,24303518,19557720,9719186,18992981,26069747,20634758,33969096,28915698; Phenotypes: CORONARY ARTERY DISSECTION SPONTANEOUS MIM#122455, POLYCYSTIC KIDNEY DISEASE 1 WITH OR WITHOUT POLYCYSTIC LIVER DISEASE, PKD1 MIM#173900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Spontaneous coronary artery dissection v0.53 COL3A1 Stephanie Hesselson reviewed gene: COL3A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 39130004; Phenotypes: CORONARY ARTERY DISSECTION, SPONTANEOUS MIM#122455; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Spontaneous coronary artery dissection v0.53 FLNA Kunal Verma reviewed gene: FLNA: Rating: AMBER; Mode of pathogenicity: None; Publications: 34863227; Phenotypes: Spontaneous coronary artery dissection; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Spontaneous coronary artery dissection v0.52 Zornitza Stark Panel status changed from internal to public
Panel types changed to Victorian Clinical Genetics Services; Rare Disease
Spontaneous coronary artery dissection v0.51 YY1AP1 Zornitza Stark reviewed gene: YY1AP1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Grange syndrome, MIM# 602531; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Spontaneous coronary artery dissection v0.51 TGFBR1 Zornitza Stark reviewed gene: TGFBR1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Loeys-Dietz syndrome 1, MIM# 609192; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Spontaneous coronary artery dissection v0.51 MYLK Zornitza Stark Marked gene: MYLK as ready
Spontaneous coronary artery dissection v0.51 MYLK Zornitza Stark Gene: mylk has been classified as Amber List (Moderate Evidence).
Spontaneous coronary artery dissection v0.51 MYLK Zornitza Stark reviewed gene: MYLK: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Aortic aneurysm, familial thoracic 7 MIM#613780; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Spontaneous coronary artery dissection v0.51 LOX Zornitza Stark reviewed gene: LOX: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Aortic aneurysm, familial thoracic 10 MIM#617168; Mode of inheritance: None
Spontaneous coronary artery dissection v0.51 LMX1B Zornitza Stark Classified gene: LMX1B as Red List (low evidence)
Spontaneous coronary artery dissection v0.51 LMX1B Zornitza Stark Gene: lmx1b has been classified as Red List (Low Evidence).
Spontaneous coronary artery dissection v0.50 LMX1B Zornitza Stark reviewed gene: LMX1B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Nail-patella syndrome MIM#161200; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Spontaneous coronary artery dissection v0.50 FLNA Zornitza Stark reviewed gene: FLNA: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: periventricular heterotopia 1 MIM#300049; Mode of inheritance: None
Spontaneous coronary artery dissection v0.50 TLN1 Ain Roesley changed review comment from: PMID: 30888838
10x families with a single affected, all missense
5x unknown inheritance
5x inherited from n unaffected parent

1x 2 generational fam with an unaffected obligate carrier, missense variant

variants reported and their counts in gnomad v4:
Ala2013Thr 1091 hets 1 hom
Arg297His 97 hets
Thr585Met 36 hets
Pro942Leu 62 hets
Ala1219Val 44 hets
Arg1241Trp 13 hets
Ser1333Thr absent
Val1964Ile 185 hets
Thr2098Met 358 hets
Val2440Glu absent

PMID: 36103205
2x individual however only 1 has a personal history of R-SCAD
Ala1574Val

Sources: Literature; to: PMID: 30888838
10x families with a single affected, all missense
5x unknown inheritance
5x inherited from an unaffected parent

1x 2 generational fam with an unaffected obligate carrier, missense variant

variants reported and their counts in gnomad v4:
Ala2013Thr 1091 hets 1 hom
Arg297His 97 hets
Thr585Met 36 hets
Pro942Leu 62 hets
Ala1219Val 44 hets
Arg1241Trp 13 hets
Ser1333Thr absent
Val1964Ile 185 hets
Thr2098Met 358 hets
Val2440Glu absent

PMID: 36103205
2x individual however only 1 has a personal history of R-SCAD
Ala1574Val

Sources: Literature
Spontaneous coronary artery dissection v0.50 LMX1B Ain Roesley Publications for gene: LMX1B were set to 37979122; 29650765
Spontaneous coronary artery dissection v0.49 LMX1B Ain Roesley Classified gene: LMX1B as Amber List (moderate evidence)
Spontaneous coronary artery dissection v0.49 LMX1B Ain Roesley Gene: lmx1b has been classified as Amber List (Moderate Evidence).
Spontaneous coronary artery dissection v0.48 LMX1B Ain Roesley edited their review of gene: LMX1B: Changed rating: AMBER; Changed publications: 29650765; Changed phenotypes: Nail-patella syndrome MIM#161200
Spontaneous coronary artery dissection v0.48 LMX1B Ain Roesley changed review comment from: PMID: 37979122; listed as "likely monogenic disease effect"

However, only a single patient found in literature
PMID: 29650765; 1x individual with SCAD and an NMD fs

this gene is constraint for LoF in gnomad v4 with only 2 hets for an NMD variant.

amber so as to not miss a diagnosis
Sources: Literature; to:
PMID: 29650765; 1x individual with SCAD and an NMD fs

this gene is constraint for LoF in gnomad v4 with only 2 hets for an NMD variant.

amber so as to not miss a diagnosis
Sources: Literature
Spontaneous coronary artery dissection v0.48 LMX1B Ain Roesley changed review comment from: PMID: 37979122; listed as "likely monogenic disease effect"

However, only a single patient found in literature
PMID: 29650765; 1x individual with SCAD and an NMD fs
Sources: Literature; to: PMID: 37979122; listed as "likely monogenic disease effect"

However, only a single patient found in literature
PMID: 29650765; 1x individual with SCAD and an NMD fs

this gene is constraint for LoF in gnomad v4 with only 2 hets for an NMD variant.

amber so as to not miss a diagnosis
Sources: Literature
Spontaneous coronary artery dissection v0.48 YY1AP1 Ain Roesley Publications for gene: YY1AP1 were set to
Spontaneous coronary artery dissection v0.47 YY1AP1 Ain Roesley Classified gene: YY1AP1 as Amber List (moderate evidence)
Spontaneous coronary artery dissection v0.47 YY1AP1 Ain Roesley Gene: yy1ap1 has been classified as Amber List (Moderate Evidence).
Spontaneous coronary artery dissection v0.46 YY1AP1 Ain Roesley edited their review of gene: YY1AP1: Changed rating: AMBER; Changed publications: 33125268
Spontaneous coronary artery dissection v0.46 YY1AP1 Ain Roesley changed review comment from:
PMID: 33125268
1x individual with a canonical splice + 1x protein truncating variant. However, phasing could not be performed

no other literature found
Sources: Literature; to:
PMID: 33125268
1x individual with a canonical splice + 1x protein truncating variant. However, phasing could not be performed

no other literature found

amber so as to not miss a diagnosis
Sources: Literature
Spontaneous coronary artery dissection v0.46 YY1AP1 Ain Roesley changed review comment from: PMID: 37979122; listed as "likely monogenic disease effect"

PMID: 33125268 was cited in paper above.
1x individual with a canonical splice + 1x protein truncating variant. However, phasing could not be performed

no other literature found
Sources: Literature; to:
PMID: 33125268
1x individual with a canonical splice + 1x protein truncating variant. However, phasing could not be performed

no other literature found
Sources: Literature
Spontaneous coronary artery dissection v0.46 PTGIR Ain Roesley Publications for gene: PTGIR were set to 32531060; 37979122
Spontaneous coronary artery dissection v0.45 PTGIR Ain Roesley changed review comment from: PMID: 37979122; listed as "likely monogenic disease effect"

PMID: 32531060; searched for 'rare' LoF variants in individuals with fibromuscular dysplasia.
However, this gene is NOT LoF constraint in gnomad v4.
200 hets for an NMD variant
Sources: Literature; to: PMID: 32531060; searched for 'rare' LoF variants in individuals with fibromuscular dysplasia.
However, this gene is NOT LoF constraint in gnomad v4.
200 hets for an NMD variant

All other papers cited PMID: 32531060
Sources: Literature
Spontaneous coronary artery dissection v0.45 TLN1 Ain Roesley Publications for gene: TLN1 were set to 30888838; 37979122
Spontaneous coronary artery dissection v0.44 TLN1 Ain Roesley edited their review of gene: TLN1: Changed publications: 30888838, 36103205
Spontaneous coronary artery dissection v0.44 TLN1 Ain Roesley changed review comment from: PMID: 37979122; listed as "likely monogenic disease effect"

but AMBER rating
10 unique rare heterozygous missense variants in 11 individuals were identified in a 2 generation SCAD family and 56 unrelated individuals with sporadic SCAD. All variants had a MAF of less than 0.06% and occurred within highly conserved β-integrin, F-actin, or vinculin binding domains. Incomplete penetrance was evident in the familial case and five individuals with unaffected heterozygous parents. No functional assays were conducted.
Sources: Literature; to: PMID: 30888838
10x families with a single affected, all missense
5x unknown inheritance
5x inherited from n unaffected parent

1x 2 generational fam with an unaffected obligate carrier, missense variant

variants reported and their counts in gnomad v4:
Ala2013Thr 1091 hets 1 hom
Arg297His 97 hets
Thr585Met 36 hets
Pro942Leu 62 hets
Ala1219Val 44 hets
Arg1241Trp 13 hets
Ser1333Thr absent
Val1964Ile 185 hets
Thr2098Met 358 hets
Val2440Glu absent

PMID: 36103205
2x individual however only 1 has a personal history of R-SCAD
Ala1574Val

Sources: Literature
Spontaneous coronary artery dissection v0.44 TGFBR2 Ain Roesley Publications for gene: TGFBR2 were set to 30071989; 27879313
Spontaneous coronary artery dissection v0.43 TGFBR2 Ain Roesley edited their review of gene: TGFBR2: Changed publications: 32897753, 35092149, 36103205; Changed phenotypes: Loeys-Dietz syndrome 2 MIM#610168
Spontaneous coronary artery dissection v0.43 TGFBR2 Ain Roesley changed review comment from: "Definitive" by ClinGen Aortopathy working group.

Reviewed in PMID 27879313 (265 cases with variants in TGFBR2).
Sources: Literature; to: PMID: 32897753
3x individuals with 2x missense and 1x +5G splice
both missense variants are absent in gnomad v4
reported SCADs: circumflex coronary artery, right descending posterior coronary artery and cervico-cephalic aneurysm and arterial dissection

PMID: 35092149
2x individuals from a SCAD cohort, however both without variant information

PMID: 36103205
3x SCAD individuals with 2x missense variants
p.Val387Leu has 569 hets + 1 hom in gnomad v4
p.Ala531Thr has 3 hets


Sources: Literature
Spontaneous coronary artery dissection v0.43 TGFBR1 Ain Roesley Publications for gene: TGFBR1 were set to 36584339; 30071989; 27879313
Spontaneous coronary artery dissection v0.42 TGFBR1 Ain Roesley Classified gene: TGFBR1 as Amber List (moderate evidence)
Spontaneous coronary artery dissection v0.42 TGFBR1 Ain Roesley Gene: tgfbr1 has been classified as Amber List (Moderate Evidence).
Spontaneous coronary artery dissection v0.41 TGFBR1 Ain Roesley edited their review of gene: TGFBR1: Changed rating: AMBER; Changed publications: 35092149, 36103205; Changed phenotypes: Loeys-Dietz syndrome 1 MIM#609192
Spontaneous coronary artery dissection v0.41 TGFBR1 Ain Roesley changed review comment from: "Definitive" by ClinGen Aortopathy working group.

Reviewed in PMID 27879313 (176 cases with variants in TGFBR1).

AMBER for AR disease: PMID 36584339
Biallelic variants reported in a single family with two sibs. Presented with severe dilatation of aorta, diaphragmatic hernia, skin translucency, and profound joint laxity at birth
Sources: Radboud University Medical Center, Nijmegen; to: PMID: 35092149
1x individual with SCAD, the missense has 3 hets in gnomad v4

PMID: 36103205
1x individual with R-SCAD and fhx, however the missense has 60 hets in gnomad v4

Amber so as to not miss a diagnosis
Spontaneous coronary artery dissection v0.41 TGFB3 Ain Roesley Publications for gene: TGFB3 were set to 30071989; 25835445
Spontaneous coronary artery dissection v0.40 TGFB3 Ain Roesley edited their review of gene: TGFB3: Changed publications: 32897753
Spontaneous coronary artery dissection v0.40 TGFB3 Ain Roesley changed review comment from: Uncertain for isolated aneurysm, but causes broader connective tissue disorder phenotype. 43 patients from 11 reported with significant cardiovascular involvement, including thoracic/abdominal aortic aneurysm and dissection, and mitral valve disease. Other systemic features overlapped clinically with Loeys-Dietz, Shprintzen-Goldberg, and Marfan syndromes, including cleft palate, bifid uvula, skeletal overgrowth, cervical spine instability and clubfoot deformity
Sources: Literature; to: PMID: 32897753
4x individuals with missense, however only 3x with personal history of SCAD


Sources: Literature
Spontaneous coronary artery dissection v0.40 TGFB2 Ain Roesley Publications for gene: TGFB2 were set to 30071989; 22772371
Spontaneous coronary artery dissection v0.39 TGFB2 Ain Roesley edited their review of gene: TGFB2: Changed publications: 33125268, 36103205; Changed phenotypes: Loeys-Dietz syndrome 4 MIM#614816
Spontaneous coronary artery dissection v0.39 TGFB2 Ain Roesley changed review comment from:
PMID: 33125268:
2x missense in SCAD individuals

PMID: 36103205
3x individuals with missense, however no personal history of SCAD, only fam history

borderline amber/green

Sources: Literature; to:
PMID: 33125268:
2x missense in SCAD individuals

PMID: 36103205
1x individual with missense and peripartum SCAD


Sources: Literature
Spontaneous coronary artery dissection v0.39 TGFB2 Ain Roesley changed review comment from: "Definitive" by ClinGen Aortopathy Working Group.

PMID: 22772371: 4 families
Sources: Literature; to:
PMID: 33125268:
2x missense in SCAD individuals

PMID: 36103205
3x individuals with missense, however no personal history of SCAD, only fam history

borderline amber/green

Sources: Literature
Spontaneous coronary artery dissection v0.39 SMAD3 Ain Roesley changed review comment from: Missense variants within the MH2 domain have been suggested to exert dominant negative mechanism by disprupting the formation of homo-oligomers (PMID: 30661052) Loss-of-function proven for PTCs (PMID: 30661052)

"Definitive" by ClinGen Aortopathy working group.
Sources: Literature; to: PMID: 32897753
1x individual with SCAD, canonical splice variant

PMID: 29650765
1x individual with SCAD, missense D258H absent in gnomad v4

PMID: 33125268
2x individuals with SCAD, 1x start loss and 1x fs

PMID: 33190788
1x individual with another variant in MYH11

Sources: Literature
Spontaneous coronary artery dissection v0.39 SMAD2 Ain Roesley Publications for gene: SMAD2 were set to 29967133
Spontaneous coronary artery dissection v0.38 SMAD2 Ain Roesley edited their review of gene: SMAD2: Changed publications: 32897753, 30448172
Spontaneous coronary artery dissection v0.38 SMAD2 Ain Roesley edited their review of gene: SMAD2: Changed publications: PMID: 32897753, 30448172
Spontaneous coronary artery dissection v0.38 SMAD2 Ain Roesley changed review comment from: 9 individuals from 5 families with wide spectrum of autosomal dominant aortic and arterial aneurysmal disease combined with connective tissue disease similar to Marfan syndrome and Loeys-Dietz syndrome.
Sources: Literature; to: PMID: 32897753
3x individuals with SCAD, all missense and absent/1 het in gnomad v4

PMID: 30448172
1x individual with a missense, absent in gnomad v4

Sources: Literature
Spontaneous coronary artery dissection v0.38 MYLK Ain Roesley Publications for gene: MYLK were set to 30071989; 27586135; 21055718; 25907466
Spontaneous coronary artery dissection v0.37 MYLK Ain Roesley Classified gene: MYLK as Amber List (moderate evidence)
Spontaneous coronary artery dissection v0.37 MYLK Ain Roesley Gene: mylk has been classified as Amber List (Moderate Evidence).
Spontaneous coronary artery dissection v0.36 MYLK Ain Roesley edited their review of gene: MYLK: Changed rating: AMBER; Changed publications: 33125268; Changed phenotypes: Aortic aneurysm, familial thoracic 7 MIM#613780
Spontaneous coronary artery dissection v0.36 MYLK Ain Roesley changed review comment from: Association between variants in this gene and aortic dissection established in multiple individuals and a 5-generation family (PMID 27586135;21055718;25907466).

"Definitive" by Clingen Aortopathy Working Group.
Sources: Literature; to: PMID: 33125268
1x SCAD individual with a stop gain

1x indiv from google search (https://medwinpublishers.com/CRIJ/unraveling-the-genetic-complexity-a-case-report-of-mylk-gene-mutation-in-a-patient-with-scad.pdf)
however, the specific variant was not provided - Authors said 'a VUS was identified'

Other papers from Google cite PMID: 33125268

Red/Amber rating, amber so as to not miss a diagnosis

Sources: Literature
Spontaneous coronary artery dissection v0.36 LOX Ain Roesley Publications for gene: LOX were set to 30071989; 26838787; 30675029.
Spontaneous coronary artery dissection v0.35 LOX Ain Roesley Classified gene: LOX as Amber List (moderate evidence)
Spontaneous coronary artery dissection v0.35 LOX Ain Roesley Gene: lox has been classified as Amber List (Moderate Evidence).
Spontaneous coronary artery dissection v0.34 LOX Ain Roesley edited their review of gene: LOX: Changed rating: AMBER; Changed publications: 32897753, 36103205; Changed phenotypes: Aortic aneurysm, familial thoracic 10 MIM#617168
Spontaneous coronary artery dissection v0.34 LOX Ain Roesley changed review comment from: Reviewed as having 'strong' gene-disease association by the HTAAD working group, based on ClinGen framework (PMID: 30071989).

Missense and nonsense variants described in six unrelated families with HTAAD and functional studies of three missense variants demonstrated a reduction in LOX activity (Guo et.al. (2016); PMID: 26838787).

Two further individuals with negative family history: one individual has pathogenic nonsense variant and second individual has VUS missense variant (Renner et al. (2019); PMID: 30675029).
Sources: Literature; to: PMID: 32897753
1x with circumflex coronary artery, possibly the same individual reported in PMID: 33125268
Met298Arg is absent in gnomad

PMID: 36103205
1x however, the missense was curated as benign (97 hets in gnomad v4)

Red/Amber rating - amber so as to not miss a diagnosis

Sources: Literature
Spontaneous coronary artery dissection v0.34 FLNA Ain Roesley changed review comment from:

PMID: 32897753
1x individual with left anterior descending coronary artery

Sources: Literature

; to: borderline red/amber but amber so as to not miss a diagnosis

PMID: 32897753
1x individual with left anterior descending coronary artery

Sources: Literature
Spontaneous coronary artery dissection v0.34 FLNA Ain Roesley Phenotypes for gene: FLNA were changed from periventricular heterotopia 1 MIM#300049 to Spontaneous coronary artery dissection
Spontaneous coronary artery dissection v0.33 FLNA Ain Roesley Classified gene: FLNA as Amber List (moderate evidence)
Spontaneous coronary artery dissection v0.33 FLNA Ain Roesley Gene: flna has been classified as Amber List (Moderate Evidence).
Spontaneous coronary artery dissection v0.32 FLNA Ain Roesley edited their review of gene: FLNA: Changed publications: 32897753
Spontaneous coronary artery dissection v0.32 FLNA Ain Roesley changed review comment from: Large review of 114 patients with loss-of-function FLNA mutations with periventricular nodular heterotopia (PVNH), found that most subjects had a cardiac anomaly or vascular abnormality (64.9%). Thoracic aortic aneurysms or dilatation (TAA) were found in 18.4%, and were associated with other structural cardiac malformations in 57.1% of patients (Chen et al. 2018; PMID: 29334594).

PMID: 32897753
1x individual with left anterior descending coronary artery

Sources: Literature

; to:

PMID: 32897753
1x individual with left anterior descending coronary artery

Sources: Literature
Spontaneous coronary artery dissection v0.32 FLNA Ain Roesley edited their review of gene: FLNA: Changed rating: AMBER; Changed publications: 29334594, 32897753; Changed phenotypes: periventricular heterotopia 1 MIM#300049
Spontaneous coronary artery dissection v0.32 FLNA Ain Roesley changed review comment from: Large review of 114 patients with loss-of-function FLNA mutations with periventricular nodular heterotopia (PVNH), found that most subjects had a cardiac anomaly or vascular abnormality (64.9%). Thoracic aortic aneurysms or dilatation (TAA) were found in 18.4%, and were associated with other structural cardiac malformations in 57.1% of patients (Chen et al. 2018; PMID: 29334594).
Sources: Literature; to: Large review of 114 patients with loss-of-function FLNA mutations with periventricular nodular heterotopia (PVNH), found that most subjects had a cardiac anomaly or vascular abnormality (64.9%). Thoracic aortic aneurysms or dilatation (TAA) were found in 18.4%, and were associated with other structural cardiac malformations in 57.1% of patients (Chen et al. 2018; PMID: 29334594).

PMID: 32897753
1x individual with left anterior descending coronary artery

Sources: Literature
Spontaneous coronary artery dissection v0.32 FBN1 Ain Roesley edited their review of gene: FBN1: Changed publications: 29357934, 34842564, 35092149; Changed phenotypes: Marfan syndrome MIM#154700, familial thoracic aortic aneurysm and aortic dissection MONDO:0019625, FBN1-related
Spontaneous coronary artery dissection v0.32 FBN1 Ain Roesley changed review comment from: Dominant-negative and LoF (haploinsufficiency) have been reported as disease mechanisms (OMIM). PTV are associated with more severe MFS and with aortic events. Missense are associated with a milder MFS and less often result in aortic events (PMID: 29357934 ).

definitive by clingen curation
Sources: Literature; to: Dominant-negative and LoF (haploinsufficiency) have been reported as disease mechanisms (OMIM). PTV are associated with more severe MFS and with aortic events. Missense are associated with a milder MFS and less often result in aortic events (PMID: 29357934 ).

definitive by clingen curation

at least 3x individuals with Marfan + FBN1 variant have been reported with SCAD
PMID: 34842564, 35092149

Sources: Literature
Spontaneous coronary artery dissection v0.32 COL5A1 Ain Roesley edited their review of gene: COL5A1: Changed publications: 32938213, 35234813; Changed phenotypes: Ehlers-Danlos syndrome, classic type, 1 MIM#130000, Fibromuscular dysplasia, multifocal MIM#619329
Spontaneous coronary artery dissection v0.32 COL5A1 Ain Roesley changed review comment from: GeneReviews: 75-78% of classical EDS is caused by pathogenic variants in COL5A1. Haploinsufficiency is the more common disease mechanism whoeever, missense variants in the triple helical domain of the α1(V) or α2(V) chains are likely to have dominant-negative activity.
(https://www.ncbi.nlm.nih.gov/books/NBK1244/)

Multifocal fibromuscular dysplasia (FMDMF) is characterized histologically by medial fibroplasia and angiographically by multiple arterial stenoses with intervening mural dilations. Arterial tortuosity, macroaneurysms, dissections, and rupture may occur.

4 unrelated individuals reported, but all had the same variant, p.Gly514Ser, and haplotype analysis was consistent with founder effect. Further rare missense variants were identified in a cohort, although limited information available.
Sources: Literature; to: GeneReviews: 75-78% of classical EDS is caused by pathogenic variants in COL5A1. Haploinsufficiency is the more common disease mechanism whoeever, missense variants in the triple helical domain of the α1(V) or α2(V) chains are likely to have dominant-negative activity.
(https://www.ncbi.nlm.nih.gov/books/NBK1244/)

SCAD individuals with variants in COL5A1 have been reported
PMID: 35234813

Sources: Literature
Spontaneous coronary artery dissection v0.32 COL3A1 Ain Roesley edited their review of gene: COL3A1: Changed publications: 30071989, 32897753, 35234813
Spontaneous coronary artery dissection v0.32 COL3A1 Ain Roesley changed review comment from: Classified as Definitive by Clingen for heritable thoracic aortic aneurysm and dissection; Ehlers-Danlos syndrome, vascular type.
Sources: Literature; to: Classified as Definitive by Clingen for heritable thoracic aortic aneurysm and dissection; Ehlers-Danlos syndrome, vascular type.

Several individuals with SCAD have also been reported with variants in COL3A1
PMID: 32897753
PMID: 36103205
PMID: 35234813


Sources: Literature
Spontaneous coronary artery dissection v0.32 COL3A1 Ain Roesley edited their review of gene: COL3A1: Changed publications: 30071989, 32897753; Changed phenotypes: Ehlers-Danlos syndrome, vascular type MIM#130050
Spontaneous coronary artery dissection v0.32 TLN1 Ain Roesley changed review comment from: PMID: 37979122; listed as "likely monogenic disease effect"

but AMBER rating
10 unique rare heterozygous missense variants in 11 individuals were identified in a 2 generation SCAD family and 56 unrelated individuals with sporadic SCAD. All variants had a MAF of less than 0.06% and occurred within highly conserved β-integrin, F-actin, or vinculin binding domains. Incomplete penetrance was evident in the familial case and five individuals with sporadic SCAD from whom parental DNA was available. No functional assays were conducted.
Sources: Literature; to: PMID: 37979122; listed as "likely monogenic disease effect"

but AMBER rating
10 unique rare heterozygous missense variants in 11 individuals were identified in a 2 generation SCAD family and 56 unrelated individuals with sporadic SCAD. All variants had a MAF of less than 0.06% and occurred within highly conserved β-integrin, F-actin, or vinculin binding domains. Incomplete penetrance was evident in the familial case and five individuals with unaffected heterozygous parents. No functional assays were conducted.
Sources: Literature
Spontaneous coronary artery dissection v0.32 YY1AP1 Ain Roesley Marked gene: YY1AP1 as ready
Spontaneous coronary artery dissection v0.32 YY1AP1 Ain Roesley Gene: yy1ap1 has been classified as Red List (Low Evidence).
Spontaneous coronary artery dissection v0.32 YY1AP1 Ain Roesley edited their review of gene: YY1AP1: Changed publications: 37979122, 33125268
Spontaneous coronary artery dissection v0.32 YY1AP1 Ain Roesley gene: YY1AP1 was added
gene: YY1AP1 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: YY1AP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: YY1AP1 were set to Grange syndrome, MIM# 602531
Review for gene: YY1AP1 was set to RED
gene: YY1AP1 was marked as current diagnostic
Added comment: PMID: 37979122; listed as "likely monogenic disease effect"

PMID: 33125268 was cited in paper above.
1x individual with a canonical splice + 1x protein truncating variant. However, phasing could not be performed

no other literature found
Sources: Literature
Spontaneous coronary artery dissection v0.31 PKD1 Ain Roesley Publications for gene: PKD1 were set to 35630097; 26798684; 26971055
Spontaneous coronary artery dissection v0.30 PKD1 Ain Roesley edited their review of gene: PKD1: Changed publications: 35630097, 26798684, 26971055, 29650765; Changed phenotypes: Polycystic kidney disease 1 MIM#173900
Spontaneous coronary artery dissection v0.30 PKD1 Ain Roesley changed review comment from: PMID: 37979122; listed as "likely monogenic disease effect"


Multiple reports of SCAD in ADPKD individuals. However, genetics analysis were not performed in any of them. (PMID: 35630097, 26798684, 26971055)

PMID: 35630097; Manuscript also reviews spontaneous ICA dissection with ADPKD but no variants
Sources: Literature; to: PMID: 37979122; listed as "likely monogenic disease effect"

Multiple reports of SCAD in ADPKD individuals. However, genetics analysis were not performed in any of them. (PMID: 35630097, 26798684, 26971055)

PMID: 35630097; Manuscript also reviews spontaneous ICA dissection with ADPKD but no variants
Sources: Literature

PMID: 29650765; reports 1x SCAD + ADPKD Individual with Cys37Tyr which is absent in gnomad and clinvar
Spontaneous coronary artery dissection v0.30 TSR1 Ain Roesley Marked gene: TSR1 as ready
Spontaneous coronary artery dissection v0.30 TSR1 Ain Roesley Gene: tsr1 has been classified as Red List (Low Evidence).
Spontaneous coronary artery dissection v0.30 TSR1 Ain Roesley gene: TSR1 was added
gene: TSR1 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: TSR1 was set to Unknown
Publications for gene: TSR1 were set to PMID: 31296288; 31296287; 37979122
Review for gene: TSR1 was set to RED
gene: TSR1 was marked as current diagnostic
Added comment: PMID: 37979122; listed as "likely monogenic disease effect"

PMID: 31296287 was cited by paper above.
SCAD cohort with WES performed and 'rare' variants filtered for. However, the variants have the following het counts in gnomad v4
Arg772Gln 27 hets 0 homs
Arg622Cys 45 hets 0 homs
Arg497Gln 7125 hets 33 homs
Trp556* absent
Arg499Pro absent
M1fs absent

PMID: 31296288 reviews PMID: 31296287

this gene is NOT constraint for LoF in gnomad v4 with 81 hets having an NMD nonsense hets
Sources: Literature
Spontaneous coronary artery dissection v0.29 TLN1 Ain Roesley Marked gene: TLN1 as ready
Spontaneous coronary artery dissection v0.29 TLN1 Ain Roesley Gene: tln1 has been classified as Amber List (Moderate Evidence).
Spontaneous coronary artery dissection v0.29 TLN1 Ain Roesley Classified gene: TLN1 as Amber List (moderate evidence)
Spontaneous coronary artery dissection v0.29 TLN1 Ain Roesley Gene: tln1 has been classified as Amber List (Moderate Evidence).
Spontaneous coronary artery dissection v0.28 TLN1 Ain Roesley gene: TLN1 was added
gene: TLN1 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: TLN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TLN1 were set to 30888838; 37979122
Phenotypes for gene: TLN1 were set to idiopathic spontaneous coronary artery dissection MONDO:0007385
Review for gene: TLN1 was set to AMBER
gene: TLN1 was marked as current diagnostic
Added comment: PMID: 37979122; listed as "likely monogenic disease effect"

but AMBER rating
10 unique rare heterozygous missense variants in 11 individuals were identified in a 2 generation SCAD family and 56 unrelated individuals with sporadic SCAD. All variants had a MAF of less than 0.06% and occurred within highly conserved β-integrin, F-actin, or vinculin binding domains. Incomplete penetrance was evident in the familial case and five individuals with sporadic SCAD from whom parental DNA was available. No functional assays were conducted.
Sources: Literature
Spontaneous coronary artery dissection v0.27 PTGIR Ain Roesley Marked gene: PTGIR as ready
Spontaneous coronary artery dissection v0.27 PTGIR Ain Roesley Gene: ptgir has been classified as Red List (Low Evidence).
Spontaneous coronary artery dissection v0.27 PTGIR Ain Roesley gene: PTGIR was added
gene: PTGIR was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: PTGIR was set to Unknown
Publications for gene: PTGIR were set to 32531060; 37979122
Review for gene: PTGIR was set to RED
gene: PTGIR was marked as current diagnostic
Added comment: PMID: 37979122; listed as "likely monogenic disease effect"

PMID: 32531060; searched for 'rare' LoF variants in individuals with fibromuscular dysplasia.
However, this gene is NOT LoF constraint in gnomad v4.
200 hets for an NMD variant
Sources: Literature
Spontaneous coronary artery dissection v0.26 PKD1 Ain Roesley Marked gene: PKD1 as ready
Spontaneous coronary artery dissection v0.26 PKD1 Ain Roesley Gene: pkd1 has been classified as Red List (Low Evidence).
Spontaneous coronary artery dissection v0.26 PKD1 Ain Roesley gene: PKD1 was added
gene: PKD1 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: PKD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PKD1 were set to 35630097; 26798684; 26971055
Phenotypes for gene: PKD1 were set to Polycystic kidney disease 1 MIM#173900
Review for gene: PKD1 was set to RED
gene: PKD1 was marked as current diagnostic
Added comment: PMID: 37979122; listed as "likely monogenic disease effect"


Multiple reports of SCAD in ADPKD individuals. However, genetics analysis were not performed in any of them. (PMID: 35630097, 26798684, 26971055)

PMID: 35630097; Manuscript also reviews spontaneous ICA dissection with ADPKD but no variants
Sources: Literature
Spontaneous coronary artery dissection v0.25 LMX1B Ain Roesley Marked gene: LMX1B as ready
Spontaneous coronary artery dissection v0.25 LMX1B Ain Roesley Gene: lmx1b has been classified as Red List (Low Evidence).
Spontaneous coronary artery dissection v0.25 LMX1B Ain Roesley gene: LMX1B was added
gene: LMX1B was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: LMX1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LMX1B were set to 37979122; 29650765
Phenotypes for gene: LMX1B were set to Nail-patella syndrome MIM#161200
Review for gene: LMX1B was set to RED
gene: LMX1B was marked as current diagnostic
Added comment: PMID: 37979122; listed as "likely monogenic disease effect"

However, only a single patient found in literature
PMID: 29650765; 1x individual with SCAD and an NMD fs
Sources: Literature
Spontaneous coronary artery dissection v0.24 MYLK Ain Roesley Classified gene: MYLK as Green List (high evidence)
Spontaneous coronary artery dissection v0.24 MYLK Ain Roesley Gene: mylk has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.23 MYLK Ain Roesley gene: MYLK was added
gene: MYLK was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: MYLK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYLK were set to 30071989; 27586135; 21055718; 25907466
Phenotypes for gene: MYLK were set to Aortic aneurysm, familial thoracic 7 MIM#613780
Review for gene: MYLK was set to GREEN
gene: MYLK was marked as current diagnostic
Added comment: Association between variants in this gene and aortic dissection established in multiple individuals and a 5-generation family (PMID 27586135;21055718;25907466).

"Definitive" by Clingen Aortopathy Working Group.
Sources: Literature
Spontaneous coronary artery dissection v0.22 LOX Ain Roesley Marked gene: LOX as ready
Spontaneous coronary artery dissection v0.22 LOX Ain Roesley Gene: lox has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.22 LOX Ain Roesley Classified gene: LOX as Green List (high evidence)
Spontaneous coronary artery dissection v0.22 LOX Ain Roesley Gene: lox has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.21 LOX Ain Roesley gene: LOX was added
gene: LOX was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: LOX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LOX were set to 30071989; 26838787; 30675029.
Phenotypes for gene: LOX were set to Aortic aneurysm, familial thoracic 10 MIM#617168
Review for gene: LOX was set to GREEN
gene: LOX was marked as current diagnostic
Added comment: Reviewed as having 'strong' gene-disease association by the HTAAD working group, based on ClinGen framework (PMID: 30071989).

Missense and nonsense variants described in six unrelated families with HTAAD and functional studies of three missense variants demonstrated a reduction in LOX activity (Guo et.al. (2016); PMID: 26838787).

Two further individuals with negative family history: one individual has pathogenic nonsense variant and second individual has VUS missense variant (Renner et al. (2019); PMID: 30675029).
Sources: Literature
Spontaneous coronary artery dissection v0.20 FLNA Ain Roesley Marked gene: FLNA as ready
Spontaneous coronary artery dissection v0.20 FLNA Ain Roesley Gene: flna has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.20 FLNA Ain Roesley Classified gene: FLNA as Green List (high evidence)
Spontaneous coronary artery dissection v0.20 FLNA Ain Roesley Gene: flna has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.19 FLNA Ain Roesley gene: FLNA was added
gene: FLNA was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: FLNA was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: FLNA were set to 29334594
Phenotypes for gene: FLNA were set to periventricular heterotopia 1 MIM#300049
Review for gene: FLNA was set to GREEN
gene: FLNA was marked as current diagnostic
Added comment: Large review of 114 patients with loss-of-function FLNA mutations with periventricular nodular heterotopia (PVNH), found that most subjects had a cardiac anomaly or vascular abnormality (64.9%). Thoracic aortic aneurysms or dilatation (TAA) were found in 18.4%, and were associated with other structural cardiac malformations in 57.1% of patients (Chen et al. 2018; PMID: 29334594).
Sources: Literature
Spontaneous coronary artery dissection v0.18 FBN1 Ain Roesley Marked gene: FBN1 as ready
Spontaneous coronary artery dissection v0.18 FBN1 Ain Roesley Gene: fbn1 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.18 FBN1 Ain Roesley Classified gene: FBN1 as Green List (high evidence)
Spontaneous coronary artery dissection v0.18 FBN1 Ain Roesley Gene: fbn1 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.17 FBN1 Ain Roesley gene: FBN1 was added
gene: FBN1 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: FBN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBN1 were set to 29357934
Phenotypes for gene: FBN1 were set to Marfan syndrome MIM#154700; familial thoracic aortic aneurysm and aortic dissection MONDO:0019625, FBN1-related
Review for gene: FBN1 was set to GREEN
gene: FBN1 was marked as current diagnostic
Added comment: Dominant-negative and LoF (haploinsufficiency) have been reported as disease mechanisms (OMIM). PTV are associated with more severe MFS and with aortic events. Missense are associated with a milder MFS and less often result in aortic events (PMID: 29357934 ).

definitive by clingen curation
Sources: Literature
Spontaneous coronary artery dissection v0.16 COL5A1 Ain Roesley Marked gene: COL5A1 as ready
Spontaneous coronary artery dissection v0.16 COL5A1 Ain Roesley Gene: col5a1 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.16 COL5A1 Ain Roesley Classified gene: COL5A1 as Green List (high evidence)
Spontaneous coronary artery dissection v0.16 COL5A1 Ain Roesley Gene: col5a1 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.15 COL5A1 Ain Roesley gene: COL5A1 was added
gene: COL5A1 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: COL5A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL5A1 were set to 32938213
Phenotypes for gene: COL5A1 were set to Ehlers-Danlos syndrome, classic type, 1 MIM#130000; Fibromuscular dysplasia, multifocal MIM#619329
Review for gene: COL5A1 was set to GREEN
gene: COL5A1 was marked as current diagnostic
Added comment: GeneReviews: 75-78% of classical EDS is caused by pathogenic variants in COL5A1. Haploinsufficiency is the more common disease mechanism whoeever, missense variants in the triple helical domain of the α1(V) or α2(V) chains are likely to have dominant-negative activity.
(https://www.ncbi.nlm.nih.gov/books/NBK1244/)

Multifocal fibromuscular dysplasia (FMDMF) is characterized histologically by medial fibroplasia and angiographically by multiple arterial stenoses with intervening mural dilations. Arterial tortuosity, macroaneurysms, dissections, and rupture may occur.

4 unrelated individuals reported, but all had the same variant, p.Gly514Ser, and haplotype analysis was consistent with founder effect. Further rare missense variants were identified in a cohort, although limited information available.
Sources: Literature
Spontaneous coronary artery dissection v0.14 COL3A1 Ain Roesley Marked gene: COL3A1 as ready
Spontaneous coronary artery dissection v0.14 COL3A1 Ain Roesley Gene: col3a1 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.14 COL3A1 Ain Roesley Classified gene: COL3A1 as Green List (high evidence)
Spontaneous coronary artery dissection v0.14 COL3A1 Ain Roesley Gene: col3a1 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.13 COL3A1 Ain Roesley gene: COL3A1 was added
gene: COL3A1 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: COL3A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL3A1 were set to 30071989
Phenotypes for gene: COL3A1 were set to Ehlers-Danlos syndrome, vascular type MIM#130050
Review for gene: COL3A1 was set to GREEN
gene: COL3A1 was marked as current diagnostic
Added comment: Classified as Definitive by Clingen for heritable thoracic aortic aneurysm and dissection; Ehlers-Danlos syndrome, vascular type.
Sources: Literature
Spontaneous coronary artery dissection v0.12 TGFBR2 Ain Roesley Marked gene: TGFBR2 as ready
Spontaneous coronary artery dissection v0.12 TGFBR2 Ain Roesley Gene: tgfbr2 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.12 TGFBR2 Ain Roesley Classified gene: TGFBR2 as Green List (high evidence)
Spontaneous coronary artery dissection v0.12 TGFBR2 Ain Roesley Gene: tgfbr2 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.11 TGFBR2 Ain Roesley gene: TGFBR2 was added
gene: TGFBR2 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: TGFBR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TGFBR2 were set to 30071989; 27879313
Phenotypes for gene: TGFBR2 were set to Loeys-Dietz syndrome 2 MIM#610168
Review for gene: TGFBR2 was set to GREEN
gene: TGFBR2 was marked as current diagnostic
Added comment: "Definitive" by ClinGen Aortopathy working group.

Reviewed in PMID 27879313 (265 cases with variants in TGFBR2).
Sources: Literature
Spontaneous coronary artery dissection v0.10 TGFBR1 Ain Roesley Marked gene: TGFBR1 as ready
Spontaneous coronary artery dissection v0.10 TGFBR1 Ain Roesley Gene: tgfbr1 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.10 TGFBR1 Ain Roesley Classified gene: TGFBR1 as Green List (high evidence)
Spontaneous coronary artery dissection v0.10 TGFBR1 Ain Roesley Gene: tgfbr1 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.9 TGFBR1 Ain Roesley gene: TGFBR1 was added
gene: TGFBR1 was added to Spontaneous coronary artery dissection. Sources: Radboud University Medical Center, Nijmegen
Mode of inheritance for gene: TGFBR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TGFBR1 were set to 36584339; 30071989; 27879313
Phenotypes for gene: TGFBR1 were set to Loeys-Dietz syndrome 1 MIM#609192
Review for gene: TGFBR1 was set to GREEN
gene: TGFBR1 was marked as current diagnostic
Added comment: "Definitive" by ClinGen Aortopathy working group.

Reviewed in PMID 27879313 (176 cases with variants in TGFBR1).

AMBER for AR disease: PMID 36584339
Biallelic variants reported in a single family with two sibs. Presented with severe dilatation of aorta, diaphragmatic hernia, skin translucency, and profound joint laxity at birth
Sources: Radboud University Medical Center, Nijmegen
Spontaneous coronary artery dissection v0.8 TGFB3 Ain Roesley Marked gene: TGFB3 as ready
Spontaneous coronary artery dissection v0.8 TGFB3 Ain Roesley Gene: tgfb3 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.8 TGFB3 Ain Roesley Classified gene: TGFB3 as Green List (high evidence)
Spontaneous coronary artery dissection v0.8 TGFB3 Ain Roesley Gene: tgfb3 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.7 TGFB3 Ain Roesley gene: TGFB3 was added
gene: TGFB3 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: TGFB3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TGFB3 were set to 30071989; 25835445
Phenotypes for gene: TGFB3 were set to Loeys-Dietz syndrome 5 MIM#615582
Review for gene: TGFB3 was set to GREEN
gene: TGFB3 was marked as current diagnostic
Added comment: Uncertain for isolated aneurysm, but causes broader connective tissue disorder phenotype. 43 patients from 11 reported with significant cardiovascular involvement, including thoracic/abdominal aortic aneurysm and dissection, and mitral valve disease. Other systemic features overlapped clinically with Loeys-Dietz, Shprintzen-Goldberg, and Marfan syndromes, including cleft palate, bifid uvula, skeletal overgrowth, cervical spine instability and clubfoot deformity
Sources: Literature
Spontaneous coronary artery dissection v0.6 TGFB2 Ain Roesley Marked gene: TGFB2 as ready
Spontaneous coronary artery dissection v0.6 TGFB2 Ain Roesley Gene: tgfb2 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.6 TGFB2 Ain Roesley Classified gene: TGFB2 as Green List (high evidence)
Spontaneous coronary artery dissection v0.6 TGFB2 Ain Roesley Gene: tgfb2 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.5 TGFB2 Ain Roesley gene: TGFB2 was added
gene: TGFB2 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: TGFB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TGFB2 were set to 30071989; 22772371
Phenotypes for gene: TGFB2 were set to Loeys-Dietz syndrome 4 MIM#614816
Penetrance for gene: TGFB2 were set to Complete
Review for gene: TGFB2 was set to GREEN
gene: TGFB2 was marked as current diagnostic
Added comment: "Definitive" by ClinGen Aortopathy Working Group.

PMID: 22772371: 4 families
Sources: Literature
Spontaneous coronary artery dissection v0.4 SMAD3 Ain Roesley Marked gene: SMAD3 as ready
Spontaneous coronary artery dissection v0.4 SMAD3 Ain Roesley Gene: smad3 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.4 SMAD3 Ain Roesley Classified gene: SMAD3 as Green List (high evidence)
Spontaneous coronary artery dissection v0.4 SMAD3 Ain Roesley Gene: smad3 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.3 SMAD3 Ain Roesley gene: SMAD3 was added
gene: SMAD3 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: SMAD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMAD3 were set to 21217753; 30661052; 30071989
Phenotypes for gene: SMAD3 were set to Loeys-Dietz syndrome 3, MIM# 613795
Review for gene: SMAD3 was set to GREEN
gene: SMAD3 was marked as current diagnostic
Added comment: Missense variants within the MH2 domain have been suggested to exert dominant negative mechanism by disprupting the formation of homo-oligomers (PMID: 30661052) Loss-of-function proven for PTCs (PMID: 30661052)

"Definitive" by ClinGen Aortopathy working group.
Sources: Literature
Spontaneous coronary artery dissection v0.2 SMAD2 Ain Roesley Marked gene: SMAD2 as ready
Spontaneous coronary artery dissection v0.2 SMAD2 Ain Roesley Gene: smad2 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.2 SMAD2 Ain Roesley Classified gene: SMAD2 as Green List (high evidence)
Spontaneous coronary artery dissection v0.2 SMAD2 Ain Roesley Gene: smad2 has been classified as Green List (High Evidence).
Spontaneous coronary artery dissection v0.1 SMAD2 Ain Roesley gene: SMAD2 was added
gene: SMAD2 was added to Spontaneous coronary artery dissection. Sources: Literature
Mode of inheritance for gene: SMAD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMAD2 were set to 29967133
Phenotypes for gene: SMAD2 were set to Loeys-Dietz syndrome 6, MIM# 619656
Penetrance for gene: SMAD2 were set to Complete
Review for gene: SMAD2 was set to GREEN
gene: SMAD2 was marked as current diagnostic
Added comment: 9 individuals from 5 families with wide spectrum of autosomal dominant aortic and arterial aneurysmal disease combined with connective tissue disease similar to Marfan syndrome and Loeys-Dietz syndrome.
Sources: Literature
Spontaneous coronary artery dissection v0.0 Ain Roesley Added Panel Spontaneous coronary artery dissection
Set panel types to: Victorian Clinical Genetics Services