Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000158607 | SCV000208542 | uncertain significance | not provided | 2013-11-18 | criteria provided, single submitter | clinical testing | p.Thr1157Ala (ACG>GCG): c.3469 A>G in exon 27 of the MYH7 gene (NM_000257.2). The Thr1157Ala variant in the MYH7 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Thr1157Ala was not observed in approximately 6000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Thr1157Ala results in a non-conservative amino acid substitution of a neutral, polar Threonine with a neutral, non-polar Alanine at a position that is highly conserved across species. Consequently, in silico analysis predicts Thr1157Ala is damaging to the protein structure/function. However, mutations in nearby residues have not been reported, indicating this region of the protein may be tolerant of change. With the clinical and molecular information available at this time, we cannot definitively determine if Thr1157Ala is a disease-causing mutation or a rare benign variant. The variant is found in DCM-CRDM panel(s). |
| Invitae | RCV001857568 | SCV002225675 | uncertain significance | Hypertrophic cardiomyopathy | 2022-07-11 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 181223). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1157 of the MYH7 protein (p.Thr1157Ala). |
| Ambry Genetics | RCV002460050 | SCV002618440 | uncertain significance | Cardiovascular phenotype | 2020-06-23 | criteria provided, single submitter | clinical testing | The p.T1157A variant (also known as c.3469A>G), located in coding exon 25 of the MYH7 gene, results from an A to G substitution at nucleotide position 3469. The threonine at codon 1157 is replaced by alanine, an amino acid with similar properties. This variant was reported in an individual with familial left ventricular non-compaction (LVNC), who had additional cardiac variants also detected (Mokhtar M et al. J ClinCase Rep. 2017;7:6). 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. |