Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001243813 | SCV001416996 | uncertain significance | Fanconi anemia | 2022-08-19 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1267 of the SLX4 protein (p.Arg1267Cys). This variant is present in population databases (rs201422743, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with SLX4-related conditions. ClinVar contains an entry for this variant (Variation ID: 968630). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Fulgent Genetics, |
RCV002499410 | SCV002799729 | uncertain significance | Fanconi anemia complementation group P | 2022-04-21 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003387981 | SCV004099667 | uncertain significance | not specified | 2023-09-08 | criteria provided, single submitter | clinical testing | Variant summary: BTBD12 c.3799C>T (p.Arg1267Cys) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 250286 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3799C>T in individuals affected with Fanconi Anemia and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited a clinical-significance assessment for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |