Submissions for variant NM_000257.4(MYH7):c.1274G>C (p.Gly425Ala)

dbSNP: rs1555338336

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000520540	SCV000616799	uncertain significance	not provided	2017-10-10	criteria provided, single submitter	clinical testing	The G425A variant of uncertain significance in the MYH7 gene has not been published as pathogenic or been reported as benign to our knowledge. G425A is not observed in large population cohorts (Lek et al., 2016). 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. However, the G425A variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. And although a missense variant in the same residue (G425R) and in nearby residues (A426T, A428V, A430E) have been reported in the Human Gene Mutation Database in association with HCM (Stenson et al., 2014), the pathogenicity of each of these variants has not been definitively determined.
Ambry Genetics	RCV002376958	SCV002687917	uncertain significance	Cardiovascular phenotype	2019-11-26	criteria provided, single submitter	clinical testing	The p.G425A variant (also known as c.1274G>C), located in coding exon 12 of the MYH7 gene, results from a G to C substitution at nucleotide position 1274. The glycine at codon 425 is replaced by alanine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.