Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000541710 | SCV000626423 | uncertain significance | Fanconi anemia | 2022-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 1224 of the SLX4 protein (p.Glu1224Val). This variant is present in population databases (rs566584111, gnomAD 0.1%). 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: 456312). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
| Gene |
RCV001775844 | SCV002013358 | uncertain significance | not provided | 2024-10-21 | criteria provided, single submitter | clinical testing | In silico analysis indicates that this missense variant does not alter protein structure/function; Reported as a germline variant in a pediatric patient with craniopharyngioma (PMID: 34301788); This variant is associated with the following publications: (PMID: 34301788) |
| Fulgent Genetics, |
RCV002490949 | SCV002777601 | uncertain significance | Fanconi anemia complementation group P | 2022-04-10 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004586764 | SCV005075884 | uncertain significance | not specified | 2024-04-02 | criteria provided, single submitter | clinical testing | Variant summary: SLX4 c.3671A>T (p.Glu1224Val) 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 8e-05 in 250712 control chromosomes. This frequency does not allow for any conclusion about variant significance. To our knowledge, no occurrence of c.3671A>T 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: 456312). Based on the evidence outlined above, the variant was classified as uncertain significance. |