ClinVar Miner

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

dbSNP: rs759623796
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Total submissions: 11
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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 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002530936 SCV000961592 pathogenic Ocular cystinosis; Juvenile nephropathic cystinosis; Inborn genetic diseases 2024-12-02 criteria provided, single submitter clinical testing 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). This variant is present in population databases (rs759623796, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with cystinosis (PMID: 10556299, 26266097). This variant is also known as c.1109_1131del23. ClinVar contains an entry for this variant (Variation ID: 496276). For these reasons, this variant has been classified as Pathogenic.
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
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre RCV000984254 SCV004806437 pathogenic Nephropathic cystinosis 2024-03-25 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV000984254 SCV005329277 pathogenic Nephropathic cystinosis 2023-05-20 criteria provided, single submitter clinical testing The observed frameshift c.771_793del (p.Gly258SerfsTer30) variant in CTNS gene has been reported in homozygous state in individual(s) affected with cystinosis (Chkioua L et al., 2015; Ghazi F, et. al., 2017). The p.Gly258SerfsTer30 variant is present with allele frequency 0.003% in gnomAD Exomes database. This variant has been submitted to the ClinVar database as Likely Pathogenic / Pathogenic (multiple submitters). This variant causes a frameshift starting with codon Glycine 258, changes this amino acid to Serine residue, and creates a premature Stop codon at position 30 of the new reading frame, denoted p.Gly258SerfsTer30. This variant is predicted to cause loss of normal protein function through protein truncation. Loss-of-function variants in CTNS are known to be pathogenic (Elmonem MA, et. al., 2016). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005091542 SCV005641930 pathogenic Ocular cystinosis; Juvenile nephropathic cystinosis; Nephropathic cystinosis 2024-01-24 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

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