ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.2087G>A (p.Arg696His)

gnomAD frequency: 0.00001  dbSNP: rs757728653
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001319223 SCV001509960 uncertain significance Hypertrophic cardiomyopathy 14 2024-06-03 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 696 of the MYH6 protein (p.Arg696His). This variant is present in population databases (rs757728653, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1019744). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYH6 protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002418963 SCV002726917 uncertain significance Cardiovascular phenotype 2021-08-20 criteria provided, single submitter clinical testing The p.R696H variant (also known as c.2087G>A), located in coding exon 16 of the MYH6 gene, results from a G to A substitution at nucleotide position 2087. The arginine at codon 696 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV002546065 SCV003195188 uncertain significance not provided 2023-01-19 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV002546065 SCV004564285 uncertain significance not provided 2023-01-03 criteria provided, single submitter clinical testing The MYH6 c.2087G>A; p.Arg696His variant (rs757728653), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 1019744). This variant is found in the general population with an overall allele frequency of 0.0028% (7/251442 alleles) in the Genome Aggregation Database. The arginine at codon 696 is highly conserved and computational analyses predict that this variant is deleterious (REVEL: 0.867). Due to limited information, the clinical significance of this variant is uncertain at this time.

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