Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002586623 | SCV002933613 | uncertain significance | Autoimmune lymphoproliferative syndrome type 2A | 2023-03-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 450 of the CASP10 protein (p.Arg450Gln). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CASP10-related conditions. ClinVar contains an entry for this variant (Variation ID: 1903789). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CASP10 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. |
| St. |
RCV002586623 | SCV004171423 | uncertain significance | Autoimmune lymphoproliferative syndrome type 2A | 2023-11-16 | criteria provided, single submitter | clinical testing | The CASP10 c.1349G>A (p.Arg450Gln) missense change has a maximum subpopulation frequency of 0.0029% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in the literature in individuals with autoimmune lymphoproliferative syndrome. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
| Ambry Genetics | RCV004603204 | SCV005102857 | uncertain significance | not specified | 2024-03-19 | criteria provided, single submitter | clinical testing | The c.1349G>A (p.R450Q) alteration is located in exon 9 (coding exon 8) of the CASP10 gene. This alteration results from a G to A substitution at nucleotide position 1349, causing the arginine (R) at amino acid position 450 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |