Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001041800 | SCV001205440 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2023-07-19 | criteria provided, single submitter | clinical testing | 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. 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 not expected to disrupt MYH6 protein function. ClinVar contains an entry for this variant (Variation ID: 839928). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. This variant is present in population databases (rs780842934, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1664 of the MYH6 protein (p.Arg1664Cys). |
| Ambry Genetics | RCV004986745 | SCV005451637 | uncertain significance | Cardiovascular phenotype | 2024-07-15 | criteria provided, single submitter | clinical testing | The p.R1664C variant (also known as c.4990C>T), located in coding exon 32 of the MYH6 gene, results from a C to T substitution at nucleotide position 4990. The arginine at codon 1664 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |