Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000807982 | SCV000948064 | uncertain significance | Aortic aneurysm, familial thoracic 7 | 2020-12-06 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). This variant has not been reported in the literature in individuals with MYLK-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with alanine at codon 494 of the MYLK protein (p.Gly494Ala). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and alanine. 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, |
RCV001811497 | SCV002048616 | uncertain significance | not provided | 2020-10-21 | criteria provided, single submitter | clinical testing | The MYLK c.1481G>C; p.Gly494Ala variant (rs1052992526), to our knowledge, has not been reported in the medical literature; however, this variant is listed in the ClinVar database (Variation ID: 652436). This variant is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The glycine at codon 494 is moderately conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.647). Based on the available information, the clinical significance of this variant is uncertain. |
| Ambry Genetics | RCV002390617 | SCV002701166 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2019-08-15 | criteria provided, single submitter | clinical testing | The p.G494A variant (also known as c.1481G>C), located in coding exon 8 of the MYLK gene, results from a G to C substitution at nucleotide position 1481. The glycine at codon 494 is replaced by alanine, an amino acid with 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. |