ClinVar

Description

This missense variant replaces arginine with histidine at codon 1045 of the MYH7 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with hypertrophic cardiomyopathy (PMID: 19659763, 24111713, 26914223, 27247418, 30462978, 31638223, 33241513, 33495597, 33586461, 34330286), arrhythmogenic cardiomyopathy (PMID: 30385303), and dilated cardiomyopathy (PMID: 26199943, 32041989), as well as in a few unaffected family members (PMID: 19659763, 26199943). Some of the affected individuals also carried a pathogenic variant in the same gene (PMID: 31638223) or in other cardiomyopathy-related genes (PMID: 26199943, 30385303), which suggests that this variant was probably not the primary cause of disease in these individuals. This variant has been identified in 10/282840 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Different variants occurring at the same position (p.Arg1045Cys, p.Arg1045Leu) are considered to be disease-causing, indicating that arginine at this position is important for MYH7 function (ClinVar variation ID: 177753, 42948). However, the available evidence is insufficient to determine the role of this p.Arg1045His variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.