ClinVar Miner

Submissions for variant NM_004937.3(CTNS):c.382C>T (p.Gln128Ter) (rs550254092)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000258034 SCV000919253 likely pathogenic Cystinosis 2018-11-05 criteria provided, single submitter clinical testing Variant summary: CTNS c.382C>T (p.Gln128X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. A truncation downstream of this position have been classified as pathogenic by our laboratory (c.646dupA (p.Thr216fsX12)). The variant was absent in 246268 control chromosomes (gnomAD). The variant, c.382C>T, has been reported in the literature in individuals affected with Cystinosis (Shotelersuk 1998, Town 1998, and Alcantara-Ortigoza 2013). These data indicate that the variant is likely associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One database has submitted an assessment for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Mendelics RCV000989680 SCV001140215 pathogenic Nephropathic cystinosis 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV001222090 SCV001394172 pathogenic Ocular cystinosis; Juvenile nephropathic cystinosis; Nephropathic cystinosis 2019-04-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln128*) in the CTNS gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with cystinosis (PMID: 9537412). ClinVar contains an entry for this variant (Variation ID: 267306). Loss-of-function variants in CTNS are known to be pathogenic (PMID: 9537412, 27102039). For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000258034 SCV000328207 pathogenic Cystinosis 2016-10-06 no assertion criteria provided literature only

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