ClinVar

Description

This missense variant replaces arginine with glutamine at codon 1712 in the LMM domain of the MYH7 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in over 30 individuals affected with hypertrophic cardiomyopathy (PMID: 18403758, 21511876, 23785128, 24510615, 27247418, 27532257, 28771489, 30297972, 31308319, 33495596, 33495597, 34352619, 34542152, 35026164, 35176171). It has been shown that this variant segregates with disease in over 20 affected relatives across at least 10 families (PMID: 37488328; ClinVar SCV000564455.5). This variant has been shown to have both age- and sex-dependent penetrance (PMID: 37488328). This variant has been identified in 6/282354 chromosomes in the general population by the Genome Aggregation Database (gnomAD). A different variant affecting the same codon, p.Arg1712Trp, is considered to be disease-causing (Clinvar variation ID: 14118), indicating that arginine at this position is important for MYH7 protein function. Based on the available evidence, this variant is classified as Pathogenic.