Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000813352 | SCV000953710 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2024-07-24 | 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 34 of the MYH6 protein (p.Arg34Cys). This variant is present in population databases (rs765792077, gnomAD 0.02%). 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: 656847). 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) performed at Invitae indicates that this missense variant is expected to disrupt MYH6 protein function with a positive predictive value of 80%. 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. |
| Gene |
RCV001772102 | SCV001994594 | uncertain significance | not provided | 2019-08-21 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect |
| Ambry Genetics | RCV002440770 | SCV002746499 | uncertain significance | Cardiovascular phenotype | 2024-11-18 | criteria provided, single submitter | clinical testing | The p.R34C variant (also known as c.100C>T), located in coding exon 1 of the MYH6 gene, results from a C to T substitution at nucleotide position 100. The arginine at codon 34 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant has been reported in an individual with hypertrophic cardiomyopathy and in a sudden infant death case; however, both individuals had additional cardiac variants detected (Seidelmann SB et al. Circ Cardiovasc Genet, 2017 Feb;10:[Epub ahead of print]; Neubauer J et al. Eur J Hum Genet, 2017 04;25:404-409). This amino acid position is not well 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. |