Submissions for variant NM_000257.4(MYH7):c.1970A>T (p.Lys657Met)

dbSNP: rs1064793204

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000483069	SCV000565285	uncertain significance	not provided	2017-02-06	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the MYH7 gene. The K657M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The K657M variant is not observed in large population cohorts (Lek et al., 2016; McVean et al., 2012; Exome Variant Server). The K657M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Though a substitution at the same amino acid position (K657Q) has been reported in the Human Gene Mutation Database in association with HCM (Stenson et al., 2014), the precise role of this variant in disease is also unclear. Observation in additional affected individuals, functional evidence, and segregation data are needed to clarify the pathogenicity of the K657M variant.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000770496	SCV000901941	uncertain significance	Cardiomyopathy	2017-06-02	criteria provided, single submitter	clinical testing