Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000556988 | SCV000641041 | uncertain significance | Aortic aneurysm, familial thoracic 4 | 2021-08-13 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with glutamine at codon 1473 of the MYH11 protein (p.Lys1473Gln). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamine. This variant is present in population databases (rs749181134, ExAC 0.003%). This missense change has been observed in individual(s) with clinical features of MYH11-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 375854). 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. |
Ambry Genetics | RCV002314119 | SCV000739190 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2016-04-08 | criteria provided, single submitter | clinical testing | The p.K1466Q variant (also known as c.4396A>C), located in coding exon 31 of the MYH11 gene, results from an A to C substitution at nucleotide position 4396. The lysine at codon 1466 is replaced by glutamine, an amino acid with similar properties, and is located in the coiled coil domain. Based on data from ExAC (Exome Aggregation Consortium (ExAC), Cambridge, MA (URL: http://exac.broadinstitute.org) [Accessed April 7, 2016]), the C allele has an overall frequency of <0.01% (1/106209). This amino acid position is well 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 variant remains unclear. |
CSER _CC_NCGL, |
RCV001796028 | SCV000503522 | uncertain significance | Congenital aneurysm of ascending aorta | 2016-08-01 | no assertion criteria provided | research | Found in patient having exome sequencing for an unrelated indication. No known history of thoracic aortic aneurysm(s). |