Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001866717 | SCV002119617 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2023-09-24 | 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 1662 of the MYH6 protein (p.Ala1662Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 1355033). 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. 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 | RCV002343894 | SCV002645635 | uncertain significance | Cardiovascular phenotype | 2024-05-17 | criteria provided, single submitter | clinical testing | The p.A1662V variant (also known as c.4985C>T), located in coding exon 32 of the MYH6 gene, results from a C to T substitution at nucleotide position 4985. The alanine at codon 1662 is replaced by valine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and valine 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. |
Ce |
RCV003426220 | SCV004129063 | likely benign | not provided | 2022-06-01 | criteria provided, single submitter | clinical testing | MYH6: BP4 |