Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000538883 | SCV000648235 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2024-10-18 | 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 860 of the MYH6 protein (p.Arg860Cys). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with restrictive cardiomyopathy or hypertrophic cardiomyopathy (PMID: 25351510, 29907873). ClinVar contains an entry for this variant (Variation ID: 470516). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. |
| Ambry Genetics | RCV000618044 | SCV000735526 | uncertain significance | Cardiovascular phenotype | 2024-01-25 | criteria provided, single submitter | clinical testing | The p.R860C variant (also known as c.2578C>T), located in coding exon 19 of the MYH6 gene, results from a C to T substitution at nucleotide position 2578. The arginine at codon 860 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 alteration remains unclear. |
| Fulgent Genetics, |
RCV002483462 | SCV002782707 | uncertain significance | Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to | 2021-08-12 | criteria provided, single submitter | clinical testing | |
| Stanford Center for Inherited Cardiovascular Disease, |
RCV000786371 | SCV000925179 | uncertain significance | not provided | 2017-05-09 | no assertion criteria provided | provider interpretation | Given that this variant has not been reported in the literature, and its uncertain association with hypertrophic cardiomyopathy, we consider this variant a variant of uncertain significance and we do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). This variant has not been reported in the literature. It is not present in ClinVar. The arginine at codon 860 is not conserved across species, and neither are neighboring amino acids. The variant was reported online in 1 of 123,131 individuals in the Genome Aggregation Consortium Dataset (gnomAD; http://gnomad.broadinstitute.org/), which currently includes variant calls on >140,000 unrelated individuals of African, Asian, European, Ashkenazi, Latino descent. Specifically, the variant was observed in 1 of 55,855 individuals of European descent (MAF=0.0009%). The phenotype of those individuals is not publicly available. The dataset is comprised of multiple cohorts, some of which were recruited from the general population, others were enriched for common cardiovascular disease. |