Cardiomyopathy_Paediatric

Gene: FHOD3

Green List (high evidence)

PMID: 32335906:
- Deletions of exon 15 or 15+16 reported in HCM families, expected to be in-frame.
- Also listed two c.1646+1 SNVs from other literature, predicted to skip exon 12. Exon 12 is in-frame.

PMID: 33586461:
- c.1286+2delT reported as pathogenic in 4 fams with HCM. (It is within intron 11, exon 11 is in-trame.)

Insufficient evidence for LoF being the disease mech for this gene. Several NMD-pred variants have been reported in patients with cardiac conditions, however they had conflicting classifications in the literature: eg.
- PMID: 33586461: Q437X, 1x HCM, LP.
- PMID: 30442288: Lys1433Serfs*10: 1x HCM, VUS, who also has an missense in MYBPC3 (VUS in ClinVar); Lys371*: 1x DCM, VUS; Lys1140*: 1x control, VUS.
- PMID: 28991257: Q859X, 1x left ventricular outflow tract obstruction (LVO), also has a stopgain in GAREM1 (gene-disease association unclear), from the Pediatric Cardiac Genomics Consortium (PCGC) cohort.

Created: 24 Oct 2022, 11:38 p.m. | Last Modified: 24 Oct 2022, 11:38 p.m.

Panel Version: 0.166

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• 32335906
• 33586461
• 30442288
• 28991257

Mode of pathogenicity
Other

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

PMID: 32335906;
Deletion of exon 15-16 in 3 families

PMID: 31742804
- 7 affecteds in a 3-generation family, het for p.(Ser527del)
- 1 genotype positive, phenotype negative family member
- 3 other SNVs associated with heart development and morphogenesis were identified in the proband but were absent in the other affected subjects

PMID: 30442288;
- 60 HCM probands with no other variants in other sarcomeric genes
- segregation of likely path/path variants were definitive/likely in 17 families (4 of which are part of a large pedigree)

Created: 1 Jul 2021, 10:11 a.m. | Last Modified: 1 Jul 2021, 10:11 a.m.

Panel Version: 0.93

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cardiomyopathy, familial hypertrophic, 28, MIM# 619402

Publications

• 32335906
• 31742804
• 30442288

Green List (high evidence)

PMID: 32335906;
Deletion of exon 15-16 in 3 families

PMID: 31742804
- 7 affecteds in a 3-generation family, het for p.(Ser527del)
- 1 genotype positive, phenotype negative family member
- 3 other SNVs associated with heart development and morphogenesis were identified in the proband but were absent in the other affected subjects

PMID: 30442288;
- 60 HCM probands with no other variants in other sarcomeric genes
- segregation of likely path/path variants were definitive/likely in 17 families (4 of which are part of a large pedigree)
Sources: Literature

Created: 29 Jul 2020, 2:25 a.m. | Last Modified: 29 Jul 2020, 2:25 a.m.

Panel Version: 0.89

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Hypertrophic cardiomyopathy

Publications

• 32335906
• 31742804
• 30442288