Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mendelics | RCV000989333 | SCV001139620 | likely pathogenic | Marfan syndrome | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001053366 | SCV001217624 | pathogenic | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2021-08-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly560 amino acid residue in FBN1. Other variant(s) that disrupt this residue have been observed in individuals with FBN1-related conditions (PMID: 11700157, 25101912), which suggests that this may be a clinically significant amino acid residue. 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. This variant has been observed to be de novo in an individual affected with Marfan syndrome (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with valine at codon 560 of the FBN1 protein (p.Gly560Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. |
Greenwood Genetic Center Diagnostic Laboratories, |
RCV000989333 | SCV005200831 | likely pathogenic | Marfan syndrome | 2024-05-28 | criteria provided, single submitter | clinical testing | PM1_Supporting, PM2, PM5_Supporting, PP2, PP3 |