Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000467280 | SCV000546285 | uncertain significance | Hypertrophic cardiomyopathy | 2023-11-13 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 295 of the MYH7 protein (p.Pro295Thr). This variant is present in population databases (no rsID available, gnomAD 0.007%). This missense change has been observed in individual(s) with congenital muscular dystrophy (Invitae). ClinVar contains an entry for this variant (Variation ID: 407203). 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 MYH7 protein function with a positive predictive value of 95%. 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 | RCV002374766 | SCV002684327 | uncertain significance | Cardiovascular phenotype | 2021-05-28 | criteria provided, single submitter | clinical testing | The p.P295T variant (also known as c.883C>A), located in coding exon 8 of the MYH7 gene, results from a C to A substitution at nucleotide position 883. The proline at codon 295 is replaced by threonine, an amino acid with highly similar properties. This alteration is located in the myosin head domain, which contains a statistically significant clustering of pathogenic missense variants (Homburger JR et al. Proc Natl Acad Sci U S A, 2016 06;113:6701-6; Walsh R et al. Genet Med, 2017 02;19:192-203; Ambry internal data). 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. |