Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001038631 | SCV001202110 | uncertain significance | Aortic aneurysm, familial thoracic 7 | 2023-12-19 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 952 of the MYLK protein (p.Asp952Asn). 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 MYLK-related conditions. ClinVar contains an entry for this variant (Variation ID: 837324). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MYLK protein function. 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 | RCV002434442 | SCV002745829 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-06-29 | criteria provided, single submitter | clinical testing | The p.D952N variant (also known as c.2854G>A), located in coding exon 15 of the MYLK gene, results from a G to A substitution at nucleotide position 2854. The aspartic acid at codon 952 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, asparagine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |