Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000543831 | SCV000626217 | uncertain significance | Fanconi anemia | 2017-04-07 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with methionine at codon 257 of the FANCA protein (p.Val257Met). The valine residue is weakly conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a FANCA-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. |