Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000792568 | SCV000931873 | uncertain significance | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2018-12-27 | criteria provided, single submitter | clinical testing | This variant has been observed in an individual with clinical features consistent with Marfan Syndrome (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. The observation of one or more missense substitutions at this codon (p.Asp1197Val and p.Asp1197His) in affected individuals suggests that this may be a clinically significant residue (PMID: 19293843, Invitae). 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. This sequence change replaces aspartic acid with valine at codon 1197 of the FBN1 protein (p.Asp1197Val). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and valine. This variant is not present in population databases (ExAC no frequency). |