Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001047328 | SCV001211278 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2019-04-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 604 of the MYH6 protein (p.Glu604Lys). The glutamic acid residue is weakly 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. 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: "Tolerated"; 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. |
| Ambry Genetics | RCV004639441 | SCV005143033 | uncertain significance | Cardiovascular phenotype | 2024-06-21 | criteria provided, single submitter | clinical testing | The p.E604K variant (also known as c.1810G>A), located in coding exon 13 of the MYH6 gene, results from a G to A substitution at nucleotide position 1810. The glutamic acid at codon 604 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |