Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000524595 | SCV000627878 | likely pathogenic | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2017-05-26 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with tryptophan at codon 985 of the FBN1 protein (p.Gly985Trp). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and tryptophan. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a FBN1-related disease. Family studies have indicated that this variant was not present in the parents of an individual with an FBN1-related disease, which suggests that it was de novo in that affected individual (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). In summary, this variant is a novel missense change with uncertain impact on protein function that has been observed to arise de novo in an affected individual. For these reasons, this variant has been classified as Likely Pathogenic. |