Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000326425 | SCV000395364 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000916250 | SCV001061485 | likely benign | Aortic aneurysm, familial thoracic 4 | 2023-03-28 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000326425 | SCV001345232 | likely benign | Familial thoracic aortic aneurysm and aortic dissection | 2019-01-04 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000916250 | SCV001473514 | uncertain significance | Aortic aneurysm, familial thoracic 4 | 2020-04-14 | criteria provided, single submitter | clinical testing | The MYH11 c.2665A>C; p.Lys889Gln variant (rs762308378) is reported in the literature in an individual affected with thoracic aortic aneurysm (Prapa 2013). This variant is reported in ClinVar (Variation ID: 318164), and is found in the South Asian population with an allele frequency of 0.23% (71/30616 alleles, including a single homozygote) in the Genome Aggregation Database. The lysine at codon 889 is moderately conserved, and computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. While the high population frequency in South Asians suggests that this is likely a benign variant, given the lack of clinical and functional data, the significance of the p.Lys889Gln variant is uncertain at this time. References: Prapa S. Bicuspid aortic valve and associated aortopathy: a combined biomechanics, histological and genetic analysis. PhD thesis, Imperial College London, London. 2013. |
Ambry Genetics | RCV000326425 | SCV002743833 | likely benign | Familial thoracic aortic aneurysm and aortic dissection | 2022-04-09 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |