Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001228706 | SCV001401121 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2019-10-31 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with isoleucine at codon 1935 of the MYH6 protein (p.Met1935Ile). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is present in population databases (rs372265811, ExAC 0.003%). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 | RCV002356976 | SCV002647398 | uncertain significance | Cardiovascular phenotype | 2022-05-02 | criteria provided, single submitter | clinical testing | The p.M1935I variant (also known as c.5805G>T), located in coding exon 37 of the MYH6 gene, results from a G to T substitution at nucleotide position 5805. The methionine at codon 1935 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. 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. |