Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002995795 | SCV003297177 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2022-04-08 | 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. 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1127 of the MYH6 protein (p.Glu1127Lys). |
| Ambry Genetics | RCV004642098 | SCV005143003 | uncertain significance | Cardiovascular phenotype | 2024-05-18 | criteria provided, single submitter | clinical testing | The p.E1127K variant (also known as c.3379G>A), located in coding exon 24 of the MYH6 gene, results from a G to A substitution at nucleotide position 3379. The glutamic acid at codon 1127 is replaced by lysine, an amino acid with similar properties. This variant has been reported in a congenital heart disease cohort (Zhang Y et al. Mol Genet Genomic Med, 2022 Oct;10:e2041). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |