Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001326404 | SCV001517434 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2023-11-10 | 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 1691 of the MYH6 protein (p.Arg1691Cys). This variant is present in population databases (rs745747137, gnomAD 0.02%). This missense change has been observed in individual(s) with congenital heart disease and/or hypertrophic cardiomyopathy (PMID: 29907873, 32492895, 35993536). ClinVar contains an entry for this variant (Variation ID: 1026007). 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. |
| Fulgent Genetics, |
RCV002476534 | SCV002793674 | uncertain significance | Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to | 2021-07-26 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004035204 | SCV005018901 | uncertain significance | Cardiovascular phenotype | 2024-01-02 | criteria provided, single submitter | clinical testing | The p.R1691C variant (also known as c.5071C>T), located in coding exon 32 of the MYH6 gene, results from a C to T substitution at nucleotide position 5071. The arginine at codon 1691 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in a pediatric cardiomyopathy cohort and a hypertrophic cardiomyopathy cohort (Hayashi T et al. J Hum Genet, 2018 Sep;63:989-996; Kim HY et al. J Clin Med, 2020 Jun;9:). 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. |