Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000647043 | SCV000768830 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2024-07-03 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 789 of the MYH6 protein (p.Arg789Cys). This variant is present in population databases (rs200925880, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 537947). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MYH6 protein function. 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 | RCV002458105 | SCV002735780 | uncertain significance | Cardiovascular phenotype | 2023-03-05 | criteria provided, single submitter | clinical testing | The p.R789C variant (also known as c.2365C>T), located in coding exon 18 of the MYH6 gene, results from a C to T substitution at nucleotide position 2365. The arginine at codon 789 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species, and cysteine is the reference amino acid in other 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. |
Revvity Omics, |
RCV003133442 | SCV003815385 | uncertain significance | not provided | 2021-02-02 | criteria provided, single submitter | clinical testing |