Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000197823 | SCV000250222 | uncertain significance | not provided | 2017-09-26 | criteria provided, single submitter | clinical testing | p.Ile1809Thr (I1809T) ATT>ACT: c.5426 T>C in exon 43 of the FBN2 gene (NM_001999.3) The I1809T variant has not been published as a mutation or reported as a benign polymorphism to our knowledge. The I1809T 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. This substitution occurs at a position that is conserved across species. Furthermore, the I1809T 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. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function. However, no missense mutations in nearby residues have been reported, indicating this region of the protein maybe tolerant of change. This variant was found in TAAD,FBN2 |
Invitae | RCV000551746 | SCV000630237 | uncertain significance | Congenital contractural arachnodactyly | 2017-06-19 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with threonine at codon 1809 of the FBN2 protein (p.Ile1809Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs766034866, ExAC 0.006%). This variant has not been reported in the literature in individuals with a FBN2-related disease. ClinVar contains an entry for this variant (Variation ID: 213339). 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"). In summary, this variant has uncertain impact on FBN2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Ce |
RCV000197823 | SCV002497348 | uncertain significance | not provided | 2022-02-01 | criteria provided, single submitter | clinical testing |