Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000467014 | SCV000543726 | uncertain significance | Aortic aneurysm, familial thoracic 4 | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with serine at codon 1513 of the MYH11 protein (p.Asn1513Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with MYH11-related conditions. 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 C0"). 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. |
Color Diagnostics, |
RCV001185792 | SCV001352087 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-03-15 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with serine at codon 1513 of the MYH11 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYH11-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV001185792 | SCV002635157 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-04-19 | criteria provided, single submitter | clinical testing | The p.N1506S variant (also known as c.4517A>G), located in coding exon 31 of the MYH11 gene, results from an A to G substitution at nucleotide position 4517. The asparagine at codon 1506 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. |