Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000544003 | SCV000650534 | uncertain significance | Aortic aneurysm, familial thoracic 7 | 2023-09-27 | 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 914 of the MYLK protein (p.Asp914Asn). This variant is present in population databases (rs561148360, gnomAD 0.003%). 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: 471715). 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. 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. |
CHEO Genetics Diagnostic Laboratory, |
RCV000769332 | SCV000900710 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2016-07-25 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000544003 | SCV001159792 | uncertain significance | Aortic aneurysm, familial thoracic 7 | 2018-07-05 | criteria provided, single submitter | clinical testing | The MYLK c.2740G>A; p.Asp914Asn variant (rs561148360), to our knowledge, is not reported in the medical literature but is reported as uncertain significance in ClinVar (Variation ID: 471715). This variant is [also] absent from general population databases (1000 Genomes Project, Exome Variant Server, and 1 out of 246266 alleles in Genome Aggregation Database), indicating it is not a common polymorphism. The aspartic acid at codon 914 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Due to limited information, the clinical significance of the p.Asp914Asn variant is uncertain at this time. |
Ambry Genetics | RCV000769332 | SCV004007696 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-04-17 | criteria provided, single submitter | clinical testing | The p.D914N variant (also known as c.2740G>A), located in coding exon 15 of the MYLK gene, results from a G to A substitution at nucleotide position 2740. The aspartic acid at codon 914 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |