Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000805639 | SCV000945602 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1612 of the MYH6 protein (p.Glu1612Lys). This variant is present in population databases (no rsID available, 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: 650479). 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. |
| Ai |
RCV002223946 | SCV002501918 | uncertain significance | not provided | 2021-08-20 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002336635 | SCV002639209 | uncertain significance | Cardiovascular phenotype | 2023-10-20 | criteria provided, single submitter | clinical testing | The p.E1612K variant (also known as c.4834G>A), located in coding exon 31 of the MYH6 gene, results from a G to A substitution at nucleotide position 4834. The glutamic acid at codon 1612 is replaced by lysine, an amino acid with similar properties. This amino acid position is well 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. |
| Gene |
RCV002223946 | SCV005386236 | uncertain significance | not provided | 2024-02-23 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |