Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000523014 | SCV000620200 | uncertain significance | not provided | 2017-08-22 | criteria provided, single submitter | clinical testing | The T547M variant in the SLX4 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The T547M variant is observed in 2/32454 (0.006%) alleles from individuals of non-Finnish European background, in the ExAC dataset (Lek et al., 2016). The T547M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret T547M as a variant of uncertain significance. |
Invitae | RCV001215563 | SCV001387314 | uncertain significance | Fanconi anemia | 2024-01-06 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 547 of the SLX4 protein (p.Thr547Met). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 451488). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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, |
RCV002490916 | SCV002780868 | uncertain significance | Fanconi anemia complementation group P | 2021-11-12 | criteria provided, single submitter | clinical testing |