Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001338551 | SCV001532231 | uncertain significance | Stormorken syndrome; Combined immunodeficiency due to STIM1 deficiency; Myopathy with tubular aggregates | 2022-08-16 | criteria provided, single submitter | clinical testing | 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. 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"). ClinVar contains an entry for this variant (Variation ID: 1035654). This variant has not been reported in the literature in individuals affected with STIM1-related conditions. This variant is present in population databases (rs751520286, gnomAD 0.006%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 8 of the STIM1 protein (p.Ala8Thr). |
Revvity Omics, |
RCV003135998 | SCV003818109 | uncertain significance | not provided | 2022-03-14 | criteria provided, single submitter | clinical testing | |
Neuberg Centre For Genomic Medicine, |
RCV003339603 | SCV004046972 | uncertain significance | Immunodeficiency, common variable, 10 | criteria provided, single submitter | clinical testing | The missense variant c.22G>A (p.Ala8Thr) in STIM1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant has been reported to the ClinVar database as Uncertain Significance. The p.Ala8Thr variant is novel (not in any individuals) in 1000 Genomes and allele frequency of 0.0007955% is reported in gnomAD. The amino acid Ala at position 8 is changed to a Thr changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by PolyPhen2 and the residue is conserved across species. The amino acid change p.Ala8Thr in STIM1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as uncertain significance . |