Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000463994 | SCV000547776 | uncertain significance | Fanconi anemia | 2019-10-30 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with valine at codon 1233 of the FANCA protein (p.Ala1233Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs545742908, ExAC 0.01%) but 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). The valine 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 rare 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. |