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Mendeliome v1.2134 IGKC Bryony Thompson Marked gene: IGKC as ready
Mendeliome v1.2134 IGKC Bryony Thompson Gene: igkc has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2134 IGKC Bryony Thompson Classified gene: IGKC as Amber List (moderate evidence)
Mendeliome v1.2134 IGKC Bryony Thompson Gene: igkc has been classified as Amber List (Moderate Evidence).
Mendeliome v1.2133 IGKC Bryony Thompson gene: IGKC was added
gene: IGKC was added to Mendeliome. Sources: Expert list
Mode of inheritance for gene: IGKC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IGKC were set to https://search.clinicalgenome.org/CCID:005121
Phenotypes for gene: IGKC were set to recurrent infections associated with rare immunoglobulin isotypes deficiency MONDO:0013576
Review for gene: IGKC was set to AMBER
Added comment: Antibody Deficiencies GCEP classify gene-disease association as Limited (18/05/2021) - at least 6 probands https://search.clinicalgenome.org/CCID:005121
Sources: Expert list
Mendeliome v1.1163 GJA4 Zornitza Stark gene: GJA4 was added
gene: GJA4 was added to Mendeliome. Sources: Expert Review
somatic tags were added to gene: GJA4.
Mode of inheritance for gene: GJA4 was set to Other
Publications for gene: GJA4 were set to 33912852
Phenotypes for gene: GJA4 were set to Cavernous hemangioma, MONDO:0003155, GJA4-related
Review for gene: GJA4 was set to GREEN
Added comment: Recurrent somatic GJA4 c.121G>T (p.Gly41Cys) mutation as a driver of hepatic (n=12) and cutaneous (n=3) vascular malformations. Induced changes in cell morphology and activated serum/glucocorticoid-regulated kinase 1 (SGK1), a serine/threonine kinase known to regulate cell proliferation and apoptosis, via non-canonical activation, in lentiviral transduction of primary human endothelial cells.
Sources: Expert Review
Mendeliome v1.1117 DDRGK1 Ain Roesley Marked gene: DDRGK1 as ready
Mendeliome v1.1117 DDRGK1 Ain Roesley Gene: ddrgk1 has been classified as Green List (High Evidence).
Mendeliome v1.1117 DDRGK1 Ain Roesley Classified gene: DDRGK1 as Green List (high evidence)
Mendeliome v1.1117 DDRGK1 Ain Roesley Gene: ddrgk1 has been classified as Green List (High Evidence).
Mendeliome v1.1116 DDRGK1 Ain Roesley gene: DDRGK1 was added
gene: DDRGK1 was added to Mendeliome. Sources: Literature
founder tags were added to gene: DDRGK1.
Mode of inheritance for gene: DDRGK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDRGK1 were set to 28263186; 35377455; 35670300; 36243336
Phenotypes for gene: DDRGK1 were set to Spondyloepimetaphyseal dysplasia, Shohat type (MIM#602557)
Review for gene: DDRGK1 was set to GREEN
gene: DDRGK1 was marked as current diagnostic
Added comment: RNA and protein studies performed for the splice variant. These two variants likely represents founder variants

PMID:28263186 reported six individuals from three different families of Iraqi Jewish descent (three patients from family 1 and one individual each from families 2-4) identified with homozygous c.408+1G>A donor splice site loss-of-function mutation in DDRGK1 and presented with Shohat-type spondyloepimetaphyseal dysplasia (SEMD). It is a skeletal dysplasia that affects cartilage development.

PMID: 35670300 reported two unrelated cases of Moroccan descent identified with homozygous missense variant c.406G>A and presented with SEMD. PMID:36243336 reported an Omani female patient identified with the same homozygous variant as the Iraqi cases and was reported with SEMD.

In addition, studies on both zebrafish and mouse models confirms the physiological role of DDRGK1 in the development and maintenance of the growth plate cartilage and deficiency of DDRGK1 recapitulate the clinical phenotype of short stature and joint abnormalities observed in patients with Shohat type SEMD (PMID:28263186; PMID:35377455).
Sources: Literature
Mendeliome v0.14634 GK Zornitza Stark Marked gene: GK as ready
Mendeliome v0.14634 GK Zornitza Stark Gene: gk has been classified as Green List (High Evidence).
Mendeliome v0.14634 GK Zornitza Stark Phenotypes for gene: GK were changed from to Glycerol kinase deficiency MIM#307030; Disorders of glycerol metabolism
Mendeliome v0.14633 GK Zornitza Stark Publications for gene: GK were set to
Mendeliome v0.14632 GK Zornitza Stark Mode of inheritance for gene: GK was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.14579 SGK3 Zornitza Stark Marked gene: SGK3 as ready
Mendeliome v0.14579 SGK3 Zornitza Stark Gene: sgk3 has been classified as Red List (Low Evidence).
Mendeliome v0.13916 DGKE Zornitza Stark Marked gene: DGKE as ready
Mendeliome v0.13916 DGKE Zornitza Stark Gene: dgke has been classified as Green List (High Evidence).
Mendeliome v0.13916 DGKE Zornitza Stark Phenotypes for gene: DGKE were changed from to Nephrotic syndrome, type 7, MIM# 615008
Mendeliome v0.13915 DGKE Zornitza Stark Publications for gene: DGKE were set to
Mendeliome v0.13914 DGKE Zornitza Stark Mode of inheritance for gene: DGKE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.13913 DGKE Zornitza Stark reviewed gene: DGKE: Rating: GREEN; Mode of pathogenicity: None; Publications: 23274426, 23542698; Phenotypes: Nephrotic syndrome, type 7, MIM# 615008; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12753 TP63 Zornitza Stark Phenotypes for gene: TP63 were changed from to ADULT syndrome, OMIM #103285; Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3, OMIM #604292; Hay-Wells syndrome, OMIM #106260; Limb-mammary syndrome, OMIM #603543; Orofacial cleft 8, OMIM #618149; Rapp-Hodgkin syndrome, OMIM #129400; Split-hand/foot malformation 4, OMIM #605289
Mendeliome v0.12750 TP63 Zornitza Stark reviewed gene: TP63: Rating: GREEN; Mode of pathogenicity: None; Publications: 20556892; Phenotypes: ADULT syndrome, OMIM #103285, Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3, OMIM #604292, Hay-Wells syndrome, OMIM #106260, Limb-mammary syndrome, OMIM #603543, Orofacial cleft 8, OMIM #618149, Rapp-Hodgkin syndrome, OMIM #129400, Split-hand/foot malformation 4, OMIM #605289; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v0.12326 AGK Zornitza Stark Marked gene: AGK as ready
Mendeliome v0.12326 AGK Zornitza Stark Gene: agk has been classified as Green List (High Evidence).
Mendeliome v0.12326 AGK Zornitza Stark Phenotypes for gene: AGK were changed from to Sengers syndrome, MIM#212350; Cataract 38 MIM#614691
Mendeliome v0.12325 AGK Zornitza Stark Publications for gene: AGK were set to
Mendeliome v0.12324 AGK Zornitza Stark Mode of inheritance for gene: AGK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.12282 AGK Elena Savva reviewed gene: AGK: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 22415731, 25208612; Phenotypes: Sengers syndrome, MIM#212350, Cataract 38 MIM#614691; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.11276 KLHDC8B Zornitza Stark Phenotypes for gene: KLHDC8B were changed from to {Hodgkin lymphoma, susceptibility to} 236000
Mendeliome v0.11274 KLHDC8B Zornitza Stark reviewed gene: KLHDC8B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Hodgkin lymphoma, susceptibility to} 236000; Mode of inheritance: None
Mendeliome v0.9384 L3MBTL1 Zornitza Stark gene: L3MBTL1 was added
gene: L3MBTL1 was added to Mendeliome. Sources: Expert Review
Mode of inheritance for gene: L3MBTL1 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Publications for gene: L3MBTL1 were set to 23543057; 15123827; 30794780
Phenotypes for gene: L3MBTL1 were set to Affected tissue: myeloid lineages; Phenotype resulting from under expression: lymphoid malignancy
Review for gene: L3MBTL1 was set to RED
Added comment: Germline variation in this imprinted gene is not currently associated with disease.

Somatic deletions of 20q are associated with chronic myeloid malignancies. Aziz et al showed that a single heterozygous 20q deletion consistently resulted in the complete loss of expression of the imprinted genes L3MBTL1 and SGK2, indicative of a pathogenetic role for loss of the active paternally inherited locus. Concomitant loss of both L3MBTL1 and SGK2 dysregulated erythropoiesis and megakaryopoiesis.
Sources: Expert Review
Mendeliome v0.7599 ZPR1 Zornitza Stark gene: ZPR1 was added
gene: ZPR1 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: ZPR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZPR1 were set to 29851065
Phenotypes for gene: ZPR1 were set to Growth restriction, hypoplastic kidneys, alpecia, and distinctive facies 619321
Review for gene: ZPR1 was set to RED
Added comment: 3 families reported with growth restriction, hypoplastic kidneys, alopecia, and distinctive facies (GKAF). All were Hispanic families from the middle Rio Grande Valley. Homozygous missense identified in one family, p. Ile196Thr. Others unavailable for testing, founder effect postulated.
Sources: Literature
Mendeliome v0.6634 PGK1 Zornitza Stark Phenotypes for gene: PGK1 were changed from Phosphoglycerate kinase 1 deficiency, MIM# 300653 to Phosphoglycerate kinase 1 deficiency, MIM# 300653; MONDO:0010392
Mendeliome v0.6633 PGK1 Zornitza Stark Marked gene: PGK1 as ready
Mendeliome v0.6633 PGK1 Zornitza Stark Gene: pgk1 has been classified as Green List (High Evidence).
Mendeliome v0.6633 PGK1 Zornitza Stark Phenotypes for gene: PGK1 were changed from to Phosphoglycerate kinase 1 deficiency, MIM# 300653
Mendeliome v0.6632 PGK1 Zornitza Stark Publications for gene: PGK1 were set to
Mendeliome v0.6631 PGK1 Zornitza Stark Mode of inheritance for gene: PGK1 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.6630 PGK1 Zornitza Stark reviewed gene: PGK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 6933565, 1547346, 7577653, 9512313; Phenotypes: Phosphoglycerate kinase 1 deficiency, MIM# 300653; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mendeliome v0.5489 PIGK Zornitza Stark Phenotypes for gene: PIGK were changed from Intellectual disability; seizures; cerebellar atrophy to Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures, MIM# 618879
Mendeliome v0.5488 PIGK Zornitza Stark edited their review of gene: PIGK: Changed phenotypes: Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures, MIM# 618879
Mendeliome v0.5272 PRKG2 Arina Puzriakova gene: PRKG2 was added
gene: PRKG2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PRKG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRKG2 were set to 33106379
Phenotypes for gene: PRKG2 were set to Acromesomelic dysplasia
Review for gene: PRKG2 was set to GREEN
Added comment: - PMID: 33106379 (2020) - Distinct homozygous variants in PRKG2 identified in two unrelated individuals, both with a skeletal dysplasia associated with severe short stature due to acromesomelic limb shortening, brachydactyly, mild to moderate platyspondyly and progressively increasing metaphyseal alterations of the long bones.

Functional studies showed both variants result in NMD and disrupt the downstream MAPK signalling pathway in response to FGF2. The role of cGKII, encoded by PRKG2, in skeletal growth has been established in several animal models (references provided in paper).
Sources: Literature
Mendeliome v0.4079 PRF1 Zornitza Stark Phenotypes for gene: PRF1 were changed from to Aplastic anemia 609135; Hemophagocytic lymphohistiocytosis, familial, 2 603553; Lymphoma, non-Hodgkin 605027
Mendeliome v0.4061 PRF1 Elena Savva reviewed gene: PRF1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19487666; Phenotypes: Aplastic anemia 609135, Hemophagocytic lymphohistiocytosis, familial, 2 603553, Lymphoma, non-Hodgkin 605027; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.3728 SGK3 Zornitza Stark gene: SGK3 was added
gene: SGK3 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SGK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SGK3 were set to 31821448
Phenotypes for gene: SGK3 were set to Hypophosphatemic rickets
Review for gene: SGK3 was set to RED
Added comment: 5 individuals from one family where a splice site variant segregated with disease.
Sources: Literature
Mendeliome v0.1949 CTPS1 Zornitza Stark Phenotypes for gene: CTPS1 were changed from to Immunodeficiency 24, MIM# 615897; Recurrent/chronic bacterial and viral infections (EBV, VZV); EBV lymphoproliferation; B-cell non-Hodgkin lymphoma
Mendeliome v0.1946 CTPS1 Zornitza Stark reviewed gene: CTPS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24870241; Phenotypes: Immunodeficiency 24, MIM# 615897, Recurrent/chronic bacterial and viral infections (EBV, VZV), EBV lymphoproliferation, B-cell non-Hodgkin lymphoma; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mendeliome v0.1889 PIGK Zornitza Stark Marked gene: PIGK as ready
Mendeliome v0.1889 PIGK Zornitza Stark Gene: pigk has been classified as Green List (High Evidence).
Mendeliome v0.1889 PIGK Zornitza Stark Classified gene: PIGK as Green List (high evidence)
Mendeliome v0.1889 PIGK Zornitza Stark Gene: pigk has been classified as Green List (High Evidence).
Mendeliome v0.1888 PIGK Zornitza Stark gene: PIGK was added
gene: PIGK was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PIGK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGK were set to 32220290
Phenotypes for gene: PIGK were set to Intellectual disability; seizures; cerebellar atrophy
Review for gene: PIGK was set to GREEN
Added comment: 12 individuals from 9 unrelated families reported.
Sources: Literature
Mendeliome v0.0 PGK1 Zornitza Stark gene: PGK1 was added
gene: PGK1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: PGK1 was set to Unknown
Mendeliome v0.0 GK Zornitza Stark gene: GK was added
gene: GK was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: GK was set to Unknown
Mendeliome v0.0 DGKE Zornitza Stark gene: DGKE was added
gene: DGKE was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: DGKE was set to Unknown
Mendeliome v0.0 AGK Zornitza Stark gene: AGK was added
gene: AGK was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services
Mode of inheritance for gene: AGK was set to Unknown