ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.2768A>C (p.Glu923Ala)

gnomAD frequency: 0.00002  dbSNP: rs371709369
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000620482 SCV000740091 uncertain significance Cardiovascular phenotype 2019-12-06 criteria provided, single submitter clinical testing The p.E923A variant (also known as c.2768A>C), located in coding exon 20 of the MYH6 gene, results from an A to C substitution at nucleotide position 2768. The glutamic acid at codon 923 is replaced by alanine, an amino acid with dissimilar 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV005091796 SCV005831177 uncertain significance Hypertrophic cardiomyopathy 14 2024-07-30 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 923 of the MYH6 protein (p.Glu923Ala). This variant is present in population databases (rs371709369, gnomAD 0.004%). 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: 520328). 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 not expected to disrupt MYH6 protein function with a negative 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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV001529402 SCV001742795 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001529402 SCV001963626 uncertain significance not provided no assertion criteria provided clinical testing

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