ClinVar Miner

Submissions for variant NC_000012.12:g.121641350C>T

dbSNP: rs2136853046
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002020275 SCV002290838 likely pathogenic Combined immunodeficiency due to ORAI1 deficiency; Myopathy, tubular aggregate, 2 2022-08-31 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the STIM1 binding domain of the ORAI1 protein, which regulates calcium influx (PMID: 26138675, 23447534, 23613525). While functional studies have not been performed to directly test the effect of this variant on ORAI1 protein function, this suggests that disruption of this region of the protein is causative of disease. ClinVar contains an entry for this variant (Variation ID: 1505011). This variant has not been reported in the literature in individuals affected with ORAI1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln205*) in the ORAI1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 97 amino acid(s) of the ORAI1 protein.

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