ClinVar

Description

The p.P211L variant (also known as c.632C>T), located in coding exon 5 of the MYH7 gene, results from a C to T substitution at nucleotide position 632. The proline at codon 211 is replaced by leucine, an amino acid with similar properties. This alteration is located in the myosin head domain, which contains a statistically significant clustering of pathogenic missense variants (Homburger JR et al. Proc Natl Acad Sci U S A, 2016 06;113:6701-6; Walsh R et al. Genet Med, 2017 02;19:192-203; Ambry internal data). This variant has been detected in individuals with hypertrophic cardiomyopathy (HCM) or from HCM cohorts; however, some individuals also had additional variants detected, or gene analysis was limited (Woo A et al. Heart, 2003 Oct;89:1179-85; Mohiddin SA et al. Genet Test, 2003;7:21-7; Perrot A et al. J Mol Med (Berl), 2005 Jun;83:468-77; Gruner C et al. Circ Cardiovasc Genet, 2011 Jun;4:288-95; Walsh R et al. Genet Med, 2017 02;19:192-203). This amino acid position is not well 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.