Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002313457 | SCV000739344 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2017-10-10 | criteria provided, single submitter | clinical testing | The p.M1902I variant (also known as c.5706G>A), located in coding exon 31 of the MYLK gene, results from a G to A substitution at nucleotide position 5706. The methionine at codon 1902 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available 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. |
| Invitae | RCV002531838 | SCV002980858 | uncertain significance | Aortic aneurysm, familial thoracic 7 | 2022-05-30 | 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. 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: 520016). This variant has not been reported in the literature in individuals affected with MYLK-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1902 of the MYLK protein (p.Met1902Ile). |