Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000534838 | SCV000650519 | uncertain significance | Aortic aneurysm, familial thoracic 7 | 2023-08-14 | criteria provided, single submitter | clinical testing | 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: 471706). This variant has not been reported in the literature in individuals affected with MYLK-related conditions. This variant is present in population databases (rs757524646, gnomAD 0.006%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 699 of the MYLK protein (p.Asn699Ser). 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. |
| ARUP Laboratories, |
RCV001508502 | SCV001477629 | uncertain significance | not provided | 2020-07-02 | criteria provided, single submitter | clinical testing | The MYLK c.2096A>G; p.Asn699Ser variant (rs757524646), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 471706). This variant is found on nine chromosomes (9/383770 alleles) in the Genome Aggregation Database. The asparagine at codon 699 is moderately conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, due to limited information, the clinical significance of the p.Asn699Ser variant is uncertain at this time. |
| Mayo Clinic Laboratories, |
RCV001508502 | SCV001714704 | uncertain significance | not provided | 2020-05-21 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002420491 | SCV002730333 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-06-25 | criteria provided, single submitter | clinical testing | The p.N699S variant (also known as c.2096A>G), located in coding exon 12 of the MYLK gene, results from an A to G substitution at nucleotide position 2096. The asparagine at codon 699 is replaced by serine, 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. |