Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002313428 | SCV000739300 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2016-07-07 | criteria provided, single submitter | clinical testing | The p.G1021A variant (also known as c.3062G>C), located in coding exon 15 of the MYLK gene, results from a G to C substitution at nucleotide position 3062. The glycine at codon 1021 is replaced by alanine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs200041144. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is poorly conserved in available vertebrate species, and alanine 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. |
| Invitae | RCV001063694 | SCV001228553 | uncertain significance | Aortic aneurysm, familial thoracic 7 | 2023-05-13 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs200041144, gnomAD 0.007%). 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: 519986). This variant has not been reported in the literature in individuals affected with MYLK-related conditions. This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1021 of the MYLK protein (p.Gly1021Ala). |