ClinVar Miner

Submissions for variant NM_004937.3(CTNS):c.611ACG[1] (p.Asp205del)

dbSNP: rs760256854
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169014 SCV000220155 likely pathogenic Nephropathic cystinosis 2014-03-12 criteria provided, single submitter literature only
Invitae RCV002516526 SCV002237871 pathogenic Ocular cystinosis; Juvenile nephropathic cystinosis; Inborn genetic diseases 2023-06-11 criteria provided, single submitter clinical testing This variant is present in population databases (rs760256854, gnomAD 0.01%). This variant, c.614_616del, results in the deletion of 1 amino acid(s) of the CTNS protein (p.Asp205del), but otherwise preserves the integrity of the reading frame. This variant has been observed in individual(s) with cystinosis (PMID: 9792862, 10556299). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the CTNS protein in which other variant(s) (p.Asp205Asn) have been determined to be pathogenic (PMID: 9792862, 22528245, 28983406). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Experimental studies have shown that this variant affects CTNS function (PMID: 15128704). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 188718).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000258027 SCV002511700 pathogenic Cystinosis 2022-04-25 criteria provided, single submitter clinical testing Variant summary: CTNS c.614_616delACG (p.Asp205del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 1.2e-05 in 251348 control chromosomes. c.614_616delACG has been reported in the literature in individuals affected with Cystinosis in homozygous and compound heterozygous states. These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV000169014 SCV004212933 pathogenic Nephropathic cystinosis 2023-10-16 criteria provided, single submitter clinical testing
GeneReviews RCV000258027 SCV000328211 not provided Cystinosis no assertion provided literature only

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