Variant: NM_000257.4(MYH7):c.29G>C (p.Gly10Ala)

CA013294

181293 (ClinVar)

Gene: MYH7

Condition: cardiomyopathy

Inheritance Mode: Autosomal dominant inheritance

UUID: a142d08b-f1e5-4b89-bd72-ba459893f00b

Approved on: 2021-03-25

Published on: 2021-12-09

HGVS expressions

NM_000257.4:c.29G>C
NM_000257.4(MYH7):c.29G>C (p.Gly10Ala)
NC_000014.9:g.23433704C>G
CM000676.2:g.23433704C>G
NC_000014.8:g.23902913C>G
CM000676.1:g.23902913C>G
NC_000014.7:g.22972753C>G
NG_007884.1:g.6958G>C
ENST00000355349.4:c.29G>C
ENST00000355349.3:c.29G>C
NM_000257.3:c.29G>C

Uncertain Significance

• Met criteria codes: PM2

• Not Met criteria codes: BS4 BS3 BS1 BP5 BP2 BP4 BA1 PS3 PS1 PS2 PS4 PP1 PP3 PM5 PM6 PM1

Expert Panel

Cardiomyopathy VCEP

Criteria Specification Information

Evidence submitted by expert panel

Cardiomyopathy VCEP

The NM_000257.4(MYH7):c.29G>C (p.Gly10Ala) variant has been reported in the homozygous state in 1 infant with a complex cardiac presentation that included DCM and HCM (GeneDx pers. comm.) ; however, this data is insufficient to apply the PS4 criterion. This variant was identified in 0.002% (FAF 95% CI; 5/113546) of European chromosomes by gnomAD v2.1.1 (PM2; https://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, due to insufficient evidence, this variant is classified as uncertain significance for cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (Kelly 2018 PMID:29300372): PM2.

Met criteria codes

• PM2: This variant was identified in 0.00173% (5/113546) of European (Non-Finnish) chromosomes in gnomAD v2.1.1

Not Met criteria codes

• BS4: not observed
• BS3: none available
• BS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP5: not observed
• BP2: not observed
• BP4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BA1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS3: none available
• PS1: n/a none are P
• PS2: not observed
• PS4: Two published proband (PMID 29555771, see Table S2, PMID: 31980526) in cohort of active asymptomatic adults but described as 'affected' with no clinical details. One proband (GeneDx internal data) with complex cardiac phenotype, apparently homozygous for this variant and for another variant in a cardiomyopathy-associated gene.
• PP1: not observed
• PP3: Majority of in silico predictors favor damaging; REVEL 0.726 not met to be conservative
• PM5: n/a none are P
• PM6: not observed
• PM1: not in head domain