Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001933785 | SCV002203945 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2024-05-15 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 648 of the MYH6 protein (p.Thr648Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with structural cardiac defects (PMID: 33131162). ClinVar contains an entry for this variant (Variation ID: 1427584). 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. |
| Ambry Genetics | RCV004641807 | SCV005143009 | uncertain significance | Cardiovascular phenotype | 2024-05-31 | criteria provided, single submitter | clinical testing | The p.T648M variant (also known as c.1943C>T), located in coding exon 14 of the MYH6 gene, results from a C to T substitution at nucleotide position 1943. The threonine at codon 648 is replaced by methionine, an amino acid with similar properties. This variant has been reported in a congenital heart disease cohort (Liu H et al. Hum Mutat, 2020 Dec;41:2167-2178). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Gene |
RCV005225545 | SCV005870356 | uncertain significance | not provided | 2024-08-22 | criteria provided, single submitter | clinical testing | Reported in a proband with HLHS and a maternal cousin with HLHS (PMID: 33131162); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33131162) |