Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Diagnostics Division, |
RCV000416376 | SCV000494030 | likely pathogenic | Marfan syndrome; Congenital contractural arachnodactyly | 2016-01-01 | criteria provided, single submitter | research | |
Labcorp Genetics |
RCV001861464 | SCV002194114 | uncertain significance | Congenital contractural arachnodactyly | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine with phenylalanine at codon 982 of the FBN2 protein (p.Cys982Phe). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and phenylalanine. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FBN2 protein function. ClinVar contains an entry for this variant (Variation ID: 375300). This missense change has been observed in individual(s) with clinical features of FBN2-related disease (PMID: 29501612). This variant is not present in population databases (ExAC no frequency). |