Submissions for variant NM_000257.4(MYH7):c.2821C>A (p.Arg941Ser)

dbSNP: rs750435648

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000458807	SCV000546281	uncertain significance	Hypertrophic cardiomyopathy	2016-08-03	criteria provided, single submitter	clinical testing	In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. This variant is present in population databases (rs750435648, ExAC 0.001%) but has not been reported in the literature in individuals with a MYH7-related disease. This sequence change replaces arginine with serine at codon 941 of the MYH7 protein (p.Arg941Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine.
Color Diagnostics, LLC DBA Color Health	RCV001178873	SCV001343427	uncertain significance	Cardiomyopathy	2020-01-13	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with serine at codon 941 of the MYH7 protein. Computational prediction tool suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold ≥0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/251494 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen	RCV002510896	SCV002822122	uncertain significance	not provided	2022-12-01	criteria provided, single submitter	clinical testing	MYH7: PP2, PP3