ClinVar Miner

Submissions for variant NM_004937.3(CTNS):c.771_793del (p.Gly258fs)

dbSNP: rs759623796
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586519 SCV000698526 pathogenic Cystinosis 2017-07-05 criteria provided, single submitter clinical testing Variant summary: The variant results in the deletion of a 23 nucleotides leading to a termination codon at position 288 of CTNS. The variant was present at a low frequency in the large and broad cohorts of the ExAC project (3/121,076 chromosomes) while it was observed in multiple CTNS patients in the literature. Considering all evidence, the variant was classified as pathogenic.
Invitae RCV002530936 SCV000961592 pathogenic Ocular cystinosis; Juvenile nephropathic cystinosis; Inborn genetic diseases 2023-08-05 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. ClinVar contains an entry for this variant (Variation ID: 496276). This variant is also known as c.1109_1131del23. This premature translational stop signal has been observed in individuals with cystinosis (PMID: 10556299, 26266097). This variant is present in population databases (rs759623796, gnomAD 0.02%). This sequence change creates a premature translational stop signal (p.Gly258Serfs*30) 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).
Centogene AG - the Rare Disease Company RCV000586519 SCV001424396 pathogenic Cystinosis criteria provided, single submitter clinical testing
Johns Hopkins Genomics, Johns Hopkins University RCV000984254 SCV001573147 pathogenic Nephropathic cystinosis 2021-04-26 criteria provided, single submitter clinical testing This 23 bp deletion in CTNS has been previously reported in individuals with nephropathic cystinosis. This CTNS variant (rs759623796) is rare (<0.1%) in a large population dataset (gnomAD: 7/251296 total alleles; 0.003%; no homozygotes) and there is an entry in ClinVar. This frameshift variant results in a premature stop codon in exon 11 likely leading to nonsense-mediated decay and lack of protein production. We consider this variant to be pathogenic.
Revvity Omics, Revvity RCV003139887 SCV003819373 pathogenic not provided 2021-12-02 criteria provided, single submitter clinical testing
Baylor Genetics RCV000984254 SCV004215218 pathogenic Nephropathic cystinosis 2022-12-25 criteria provided, single submitter clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center RCV000984254 SCV004806437 pathogenic Nephropathic cystinosis 2024-03-25 criteria provided, single submitter clinical testing
Counsyl RCV000984254 SCV001132377 likely pathogenic Nephropathic cystinosis 2014-08-16 no assertion criteria provided clinical testing
Natera, Inc. RCV000586519 SCV002093236 pathogenic Cystinosis 2021-01-26 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.