Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000633613 | SCV000754860 | uncertain significance | Congenital contractural arachnodactyly | 2017-10-17 | criteria provided, single submitter | clinical testing | 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. 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 C0"). This variant has not been reported in the literature in individuals with FBN2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with cysteine at codon 2100 of the FBN2 protein (p.Arg2100Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. |
Gene |
RCV001766348 | SCV002000632 | uncertain significance | not provided | 2021-04-27 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Does not affect a cysteine residue within a calcium-binding EGF-like domain of the FBN2 gene; cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with FBN2-related disorders (Frederic et al., 2009); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 528424; Landrum et al., 2016) |