Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002006035 | SCV002270893 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2023-08-23 | criteria provided, single submitter | clinical testing | 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. 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 expected to disrupt MYH6 protein function. ClinVar contains an entry for this variant (Variation ID: 1484753). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. This variant is present in population databases (rs375142167, gnomAD 0.003%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 498 of the MYH6 protein (p.Glu498Lys). |
| Ambry Genetics | RCV002388987 | SCV002698752 | uncertain significance | Cardiovascular phenotype | 2020-01-16 | criteria provided, single submitter | clinical testing | The p.E498K variant (also known as c.1492G>A), located in coding exon 12 of the MYH6 gene, results from a G to A substitution at nucleotide position 1492. The glutamic acid at codon 498 is replaced by lysine, an amino acid with similar 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. |
| Fulgent Genetics, |
RCV002492243 | SCV002784698 | uncertain significance | Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to | 2021-10-18 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004538714 | SCV004714311 | uncertain significance | MYH6-related disorder | 2023-12-20 | no assertion criteria provided | clinical testing | The MYH6 c.1492G>A variant is predicted to result in the amino acid substitution p.Glu498Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0026% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |