Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000519486 | SCV000620135 | uncertain significance | not provided | 2022-12-21 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Invitae | RCV001853660 | SCV002213259 | uncertain significance | Aortic aneurysm, familial thoracic 7 | 2021-09-19 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with MYLK-related conditions. 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. 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 MYLK protein function. ClinVar contains an entry for this variant (Variation ID: 451436). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with lysine at codon 810 of the MYLK protein (p.Met810Lys). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and lysine. |
| Ambry Genetics | RCV002456012 | SCV002737357 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2019-08-24 | criteria provided, single submitter | clinical testing | The p.M810K variant (also known as c.2429T>A), located in coding exon 14 of the MYLK gene, results from a T to A substitution at nucleotide position 2429. The methionine at codon 810 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species; however, lysine 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. |