Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001205427 | SCV001376683 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2024-11-18 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 700 of the MYH6 protein (p.Val700Met). This variant is present in population databases (rs767142932, gnomAD 0.007%). This missense change has been observed in individual(s) with dilated cardiomyopathy and/or patent foramen ovale, however in some of these individuals another variant was also identified in a cardiomyopathy-related gene (PMID: 20656787, 30847666). ClinVar contains an entry for this variant (Variation ID: 936597). 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. |
| Ai |
RCV002223284 | SCV002501716 | uncertain significance | not provided | 2021-08-24 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002418683 | SCV002724506 | uncertain significance | Cardiovascular phenotype | 2019-10-17 | criteria provided, single submitter | clinical testing | The p.V700M variant (also known as c.2098G>A), located in coding exon 16 of the MYH6 gene, results from a G to A substitution at nucleotide position 2098. The valine at codon 700 is replaced by methionine, an amino acid with highly similar properties. This alteration was reported in a subject with congenital heart disease who also carried a missense alteration in the GATA4 gene (Granados-Riveron JT et al. Hum. Mol. Genet., 2010 Oct;19:4007-16; Granados-Riveron JT et al. Congenit Heart Dis., 2012 Oct;7:151-9). 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. |