Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001870458 | SCV002127458 | uncertain significance | Fanconi anemia | 2021-04-14 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 142 of the SLX4 protein (p.Gly142Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs773117024, ExAC 0.01%). This variant has not been reported in the literature in individuals with SLX4-related disease. 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 arginine 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. |
| Ambry Genetics | RCV002545858 | SCV003601940 | uncertain significance | Inborn genetic diseases | 2022-01-03 | criteria provided, single submitter | clinical testing | The c.424G>C (p.G142R) alteration is located in exon 2 (coding exon 1) of the SLX4 gene. This alteration results from a G to C substitution at nucleotide position 424, causing the glycine (G) at amino acid position 142 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |