Submissions for variant NM_002471.4(MYH6):c.3526A>T (p.Met1176Leu)

gnomAD frequency: 0.00002  dbSNP: rs769554911

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000477255	SCV000546163	uncertain significance	Hypertrophic cardiomyopathy 14	2016-05-01	criteria provided, single submitter	clinical testing	This sequence change replaces methionine with leucine at codon 1176 of the MYH6 protein (p.Met1176Leu). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and leucine. In summary, this variant is a rare missense change with uncertain impact on protein function. It is not expected to cause 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). While this variant is present in population databases (rs769554911), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with a MYH6-related disease.