Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001962681 | SCV002208876 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2025-02-02 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 769 of the MYH6 protein (p.Ala769Val). This variant is present in population databases (rs139182991, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. 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: 1436827). 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) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MYH6 protein function. 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 | RCV002442906 | SCV002735552 | uncertain significance | Cardiovascular phenotype | 2024-04-16 | criteria provided, single submitter | clinical testing | The p.A769V variant (also known as c.2306C>T), located in coding exon 18 of the MYH6 gene, results from a C to T substitution at nucleotide position 2306. The alanine at codon 769 is replaced by valine, an amino acid with similar properties. This variant was reported in one individual with arrhythmogenic right ventricular cardiomyopathy (ARVC); however, clinical details were limited (Lu C et al. J Transl Med, 2018 08;16:241). This alteration was also reported in a cohort of subjects with recurrent syncope (Lee SH et al. J Cardiovasc Dev Dis, 2022 Aug;9:). 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. |