Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000821823 | SCV000962595 | uncertain significance | Aortic aneurysm, familial thoracic 7 | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 622 of the MYLK protein (p.Ala622Gly). This variant is present in population databases (rs748628438, gnomAD 0.02%). 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: 663860). 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 with a negative predictive value of 80%. 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 | RCV002408986 | SCV002723383 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-06-30 | criteria provided, single submitter | clinical testing | The p.A622G variant (also known as c.1865C>G), located in coding exon 11 of the MYLK gene, results from a C to G substitution at nucleotide position 1865. The alanine at codon 622 is replaced by glycine, an amino acid with similar properties. This amino acid position is well 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. |