Hypertrophic cardiomyopathy_HCM

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)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cardiomyopathy, familial hypertrophic, 28, MIM# 619402

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