Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000822349 | SCV000963149 | uncertain significance | Aortic aneurysm, familial thoracic 4 | 2018-11-26 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with arginine at codon 574 of the MYH11 protein (p.Lys574Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MYH11-related disease. 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: "Probably Damaging"; 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. |
All of Us Research Program, |
RCV004807205 | SCV005430663 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2024-04-25 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with arginine at codon 574 of the MYH11 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 | RCV004807205 | SCV005455977 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2024-10-27 | criteria provided, single submitter | clinical testing | The p.K567R variant (also known as c.1700A>G), located in coding exon 13 of the MYH11 gene, results from an A to G substitution at nucleotide position 1700. The lysine at codon 567 is replaced by arginine, 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. Based on the available evidence, the clinical significance of this variant remains unclear. |