Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000200043 | SCV000250309 | uncertain significance | not provided | 2014-11-18 | criteria provided, single submitter | clinical testing | p.Gly2317Ser (GGC>AGC): c.6949 G>A in exon 55 of the FBN2 gene (NM_001999.3) The G2317S variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The G2317S variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G2317S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense mutations in nearby residues have not been reported, indicating this region of the protein may tolerate change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. This variant was found in TAADV2-1 |
| Invitae | RCV001242176 | SCV001415246 | uncertain significance | Congenital contractural arachnodactyly | 2023-05-22 | criteria provided, single submitter | clinical testing | 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FBN2 protein function. 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. ClinVar contains an entry for this variant (Variation ID: 213424). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2317 of the FBN2 protein (p.Gly2317Ser). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with FBN2-related conditions. |