Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000614150 | SCV000710916 | uncertain significance | not specified | 2016-08-14 | criteria provided, single submitter | clinical testing | The p.Arg1477His variant in MYH6 has not been previously reported in individuals with cardiomyopathy, but has been identified in 2/10308 African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs 147586142). Computational prediction tools and conservation analysis suggest tha t the p.Arg1477His variant may impact the protein, though this information is no t predictive enough to determine pathogenicity. In summary, the clinical signifi cance of the p.Arg1477His variant is uncertain. |
| Invitae | RCV000801070 | SCV000940827 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2018-10-14 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 1477 of the MYH6 protein (p.Arg1477His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MYH6-related disease. ClinVar contains an entry for this variant (Variation ID: 504533). This variant is present in population databases (rs147586142, ExAC 0.02%). |
| Ambry Genetics | RCV002331029 | SCV002631281 | uncertain significance | Cardiovascular phenotype | 2019-10-17 | criteria provided, single submitter | clinical testing | The p.R1477H variant (also known as c.4430G>A), located in coding exon 29 of the MYH6 gene, results from a G to A substitution at nucleotide position 4430. The arginine at codon 1477 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |