ClinVar Miner

Submissions for variant NM_000157.4(GBA):c.661C>A (p.Pro221Thr)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001199857 SCV001370592 likely pathogenic Gaucher disease 2020-06-03 criteria provided, single submitter clinical testing Variant summary: GBA c.661C>A (p.Pro221Thr, legacy name Pro182Thr) results in a non-conservative amino acid change located in the Glycosyl hydrolase family 30, TIM-barrel domain (IPR033453) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251024 control chromosomes. c.661C>A has been reported in the literature in at-least one individual affected with Gaucher Disease Type 1 (Beutler_1994) and has been subsequently cited by others (example, Duran_2012, McNeill_2012, Hruska_2008, Atrian_2008, Grabowski_1997). Additional Gaucher Disease patients with this variant have been reported as part of the GAUCHERITE study database (Donald_2019, unpublished data). As the GAUCHERITE study is a multicenter observational stratified medicine project of UK patients with a confirmed biochemical diagnosis of Gaucher disease (NCT03240653), these data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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