Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000156037 | SCV000205750 | uncertain significance | not specified | 2013-09-19 | criteria provided, single submitter | clinical testing | The Glu1688Lys variant in MYH6 has not been reported in individuals with cardiom yopathy or in large population studies. Computational analyses (biochemical amin o acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that th e Glu1688Lys variant may impact the normal function of the protein, though this information is not predictive enough to determine pathogenicity conclusively. Ad ditional information is needed to fully assess the clinical significance of the Glu1688Lys variant. |
| Labcorp Genetics |
RCV001338720 | SCV001532406 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2020-09-18 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 1688 of the MYH6 protein (p.Glu1688Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MYH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 179250). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |