Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000195638 | SCV000250307 | uncertain significance | not provided | 2018-02-21 | criteria provided, single submitter | clinical testing | p.Arg2308Lys (R2308K) AGG>AAG: c.6923 G>A in exon 55 of the FBN2 gene (NM_001999.3) The R2308K variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R2308K variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, the R2308K variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved only in mammals and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Furthermore, missense mutations in nearby residues have not been reported. Finally, the R2308K variant does not affect a Cysteine residue within a calcium-binding EGF-like domain of FBN2. Cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with CCA (Collod-Beroud et al., 2003). 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-PANCARD |