Submissions for variant NM_000257.4(MYH7):c.758G>T (p.Gly253Val) (rs730880853)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000158763	SCV000208698	likely pathogenic	not provided	2012-09-26	criteria provided, single submitter	clinical testing	p.Gly253Val (GGG>GTG):c.758 G>T in exon 9 of the MYH7 gene (NM_000257.2). The Gly253Val variant in the MYH7 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Although Gly253Val results in a conservativeamino acid substitution of one non-polar residue for another, the Gly253 residue is conserved across species. In silico analysis predicts Gly253Val is probably damaging to the protein structure/function. Mutations in nearby residues (His251Asn, Gly256Glu, Ala259Glu) have been reported in association with HCM, further supporting the functional importance of this region of the protein. Furthermore, the NHLBI ESP Exome Variant Server reports Gly253Val was not observed in approximately 6,400 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations.In summary, while Gly253Val is a good candidate for a disease-causing mutation, with the clinical and molecular information available at this time we cannot unequivocally determine the clinical significance of this variant. The variant is found in HCM panel(s).
Ambry Genetics	RCV000620876	SCV000735493	uncertain significance	Cardiovascular phenotype	2016-08-16	criteria provided, single submitter	clinical testing	Lines of evidence used in support of classification: Insufficient evidence