Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000600539 | SCV000713324 | uncertain significance | not specified | 2017-07-21 | criteria provided, single submitter | clinical testing | The p.Gln78Arg variant in MYH6 has not been previously reported in individuals w ith cardiomyopathy, but has been identified in 1/24006 African and 1/126688 Euro pean chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broad institute.org/; dbSNPrs772216708). Computational prediction tools and conservati on analysis suggest that the p.Gln78Arg variant may impact the protein, though t his information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Gln78Arg variant is uncertain. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000600539 | SCV000919830 | uncertain significance | not specified | 2018-09-11 | criteria provided, single submitter | clinical testing | Variant summary: MYH6 c.233A>G (p.Gln78Arg) results in a conservative amino acid change located in the Myosin, N-terminal, SH3-like domain of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 7.2e-06 in 277170 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.233A>G in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Gene |
RCV002291678 | SCV002584128 | uncertain significance | not provided | 2022-10-11 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD) |
| Ambry Genetics | RCV002448846 | SCV002732376 | uncertain significance | Cardiovascular phenotype | 2024-09-20 | criteria provided, single submitter | clinical testing | The p.Q78R variant (also known as c.233A>G), located in coding exon 2 of the MYH6 gene, results from an A to G substitution at nucleotide position 233. The glutamine at codon 78 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |
| Fulgent Genetics, |
RCV002483680 | SCV002793250 | uncertain significance | Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to | 2021-11-01 | criteria provided, single submitter | clinical testing |