ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.2354G>A (p.Arg785His)

gnomAD frequency: 0.00005  dbSNP: rs769341738
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000468612 SCV000546162 uncertain significance Hypertrophic cardiomyopathy 14 2024-10-13 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 785 of the MYH6 protein (p.Arg785His). This variant is present in population databases (rs769341738, 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: 407156). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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 RCV002446799 SCV002734464 uncertain significance Cardiovascular phenotype 2024-05-05 criteria provided, single submitter clinical testing The p.R785H variant (also known as c.2354G>A), located in coding exon 18 of the MYH6 gene, results from a G to A substitution at nucleotide position 2354. The arginine at codon 785 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and histidine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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