ClinVar Miner

Submissions for variant NM_004937.3(CTNS):c.561+1del

dbSNP: rs786204667
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169470 SCV000220909 likely pathogenic Nephropathic cystinosis 2014-11-24 criteria provided, single submitter literature only
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001175037 SCV001338557 likely pathogenic Cystinosis 2020-04-30 criteria provided, single submitter clinical testing Variant summary: CTNS c.561+1delG is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a cryptic 5 splicing donor site. Four predict the variant creates a 5 donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 250886 control chromosomes (gnomAD). c.561+1delG has been reported in the literature in individuals affected with Cystinosis (Town_1998, Shotelersuk_1998). These data indicate that the variant may 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.
Invitae RCV002515201 SCV001591756 pathogenic Ocular cystinosis; Juvenile nephropathic cystinosis; Inborn genetic diseases 2023-02-23 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This sequence change creates a premature translational stop signal (Splice site) in the CTNS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CTNS are known to be pathogenic (PMID: 9537412, 27102039). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with CTNS-related conditions (PMID: 9537412). This variant is also known as 900/901+1delG, 561+1del. ClinVar contains an entry for this variant (Variation ID: 189067).
Fulgent Genetics, Fulgent Genetics RCV001535992 SCV001752665 pathogenic Ocular cystinosis; Juvenile nephropathic cystinosis; Nephropathic cystinosis 2021-06-30 criteria provided, single submitter clinical testing
Baylor Genetics RCV000169470 SCV004212952 pathogenic Nephropathic cystinosis 2023-09-05 criteria provided, single submitter clinical testing

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