Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002313402 | SCV000739230 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2017-03-14 | criteria provided, single submitter | clinical testing | The p.P82T variant (also known as c.244C>A), located in coding exon 1 of the MYH11 gene, results from a C to A substitution at nucleotide position 244. The proline at codon 82 is replaced by threonine, an amino acid with highly similar properties, and is in the myosin head-like domain. 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. |
Labcorp Genetics |
RCV003629129 | SCV004518987 | uncertain significance | Aortic aneurysm, familial thoracic 4 | 2023-12-26 | 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 82 of the MYH11 protein (p.Pro82Thr). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with MYH11-related conditions. ClinVar contains an entry for this variant (Variation ID: 519948). 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 not expected to disrupt MYH11 protein function with a negative 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. |