Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000704826 | SCV000833795 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2024-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 680 of the MYH6 protein (p.Arg680Gln). This variant is present in population databases (rs551746815, gnomAD 0.008%). 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: 581101). 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 | RCV002422596 | SCV002723030 | uncertain significance | Cardiovascular phenotype | 2022-07-06 | criteria provided, single submitter | clinical testing | The p.R680Q variant (also known as c.2039G>A), located in coding exon 15 of the MYH6 gene, results from a G to A substitution at nucleotide position 2039. The arginine at codon 680 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |