ClinVar Miner

Submissions for variant NM_014140.3(SMARCAL1):c.2114C>T (p.Thr705Ile) (rs200644381)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000778915 SCV000915325 uncertain significance Schimke immunoosseous dysplasia 2017-09-13 criteria provided, single submitter clinical testing The SMARCAL1 c.2114C>T (p.Thr705Ile) missense variant has been reported in one study and is found one patient with Schimke immunoosseous dysplasia (SIOD) in a compound heterozygous state (Boerkoel et al. 2002). The patient is described as having a severe phenotype presenting with renal disease, lymphocytopenia, blood pancytopenia, central nervous symptoms, and died at 15 years old from a cerebrovascular event (Boerkoel et al. 2002). The p.Thr705Ile variant was absent from 252 control chromosomes and is reported at a frequency of 0.00035 in the European-American population of the Exome Sequencing Project. In vitro expression analysis showed reduced chromatin binding and complete nuclear localization of p.Thr705Ile, while expression in Drosophila melanogaster wings showed expression of two percent for p.Thr705Ile compared to 70% associated with wild type (Elizondo et al. 2009). Based on the evidence, the p.Thr705Ile variant is classified as a variant of unknown significance but suspicious for pathogenicity for Schimke immunoosseous dysplasia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

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