Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000630941 | SCV000751916 | uncertain significance | Fanconi anemia | 2024-11-28 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 649 of the SLX4 protein (p.Gly649Ser). This variant is present in population databases (rs780269002, gnomAD 0.02%). 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: 526415). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The serine 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, |
RCV002477379 | SCV002783566 | uncertain significance | Fanconi anemia complementation group P | 2024-03-06 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004800499 | SCV005423536 | uncertain significance | not specified | 2024-10-02 | criteria provided, single submitter | clinical testing | Variant summary: SLX4 c.1945G>A (p.Gly649Ser) 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 7.2e-05 in 250664 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in SLX4 causing Fanconi Anemia, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1945G>A in individuals affected with Fanconi Anemia and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 526415). Based on the evidence outlined above, the variant was classified as uncertain significance. |