Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000227495 | SCV000287254 | uncertain significance | Congenital contractural arachnodactyly | 2016-01-09 | criteria provided, single submitter | clinical testing | In summary, this is a novel missense change with uncertain impact on protein function. 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a FBN2-related disease. This sequence change replaces threonine with alanine at codon 847 of the FBN2 protein (p.Thr847Ala). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and alanine. |
Ambry Genetics | RCV002450684 | SCV002740070 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2018-05-30 | criteria provided, single submitter | clinical testing | The p.T847A variant (also known as c.2539A>G), located in coding exon 19 of the FBN2 gene, results from an A to G substitution at nucleotide position 2539. The threonine at codon 847 is replaced by alanine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |