Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000503960 | SCV000594651 | uncertain significance | not specified | 2017-05-25 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001063236 | SCV001228073 | uncertain significance | Fanconi anemia | 2019-12-26 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with glutamic acid at codon 101 of the FANCA protein (p.Gln101Glu). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is present in population databases (rs140412064, ExAC 0.01%). This variant has not been reported in the literature in individuals with FANCA-related disease. ClinVar contains an entry for this variant (Variation ID: 435125). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamic acid 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 and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |