Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000198753 | SCV000250151 | uncertain significance | not provided | 2015-04-03 | criteria provided, single submitter | clinical testing | p.Ile401Val (I401V) ATT>GTT: c.1201 A>G in exon 9 of the FBN2 gene (NM_001999.3) Mutations in the FBN2 gene have been reported in 27-75% of patients with autosomal dominant congenital contractural arachnodactyly, which is associated with a risk of aortic root dilatation (Godfrey M et al., 2012). The I401V variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The I401V 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 class conserved across species. However, the I401V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In silico analysis predicts this variant likely does not alter the protein structure/function. Furthermore, missense mutations in nearby residues have not been reported, indicating this region of the protein may be tolerant of 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 |