ClinVar Miner

Submissions for variant NM_004937.3(CTNS):c.18_21del (p.Thr7fs) (rs786204501)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169183 SCV000220424 pathogenic Nephropathic cystinosis 2014-06-17 criteria provided, single submitter literature only
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000723831 SCV000229059 pathogenic not provided 2015-04-24 criteria provided, single submitter clinical testing
Invitae RCV000698691 SCV000827371 pathogenic Ocular cystinosis; Juvenile nephropathic cystinosis; Nephropathic cystinosis 2019-12-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr7Phefs*7) in the CTNS gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs764835663, ExAC 0.01%). This variant has been observed as homozygous or in combination with another CTNS variant in individuals and families affected with nephropathic cystinosis (PMID: 9537412, 28276207). ClinVar contains an entry for this variant (Variation ID: 188834). Loss-of-function variants in CTNS are known to be pathogenic (PMID: 9537412, 27102039). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000258029 SCV000917266 pathogenic Cystinosis 2018-01-29 criteria provided, single submitter clinical testing Variant summary: CTNS c.18_21delGACT (p.Thr7PhefsX7) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.646dupA/p.Thr216fsX12). The variant allele was found at a frequency of 5.4e-05 in 277224 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in CTNS causing Cystinosis (5.4e-05 vs 0.0025). c.18_21delGACT has been reported in the literature in multiple individuals affected with Cystinosis. These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV000698691 SCV001163422 pathogenic Ocular cystinosis; Juvenile nephropathic cystinosis; Nephropathic cystinosis criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000723831 SCV001249975 pathogenic not provided 2018-08-01 criteria provided, single submitter clinical testing
Molecular Biology Laboratory,Fundació Puigvert RCV000169183 SCV001425072 pathogenic Nephropathic cystinosis 2020-02-01 criteria provided, single submitter research
OMIM RCV000169183 SCV000024869 pathogenic Nephropathic cystinosis 2009-11-01 no assertion criteria provided literature only
OMIM RCV000004695 SCV000024870 pathogenic Juvenile nephropathic cystinosis 2009-11-01 no assertion criteria provided literature only
GeneReviews RCV000258029 SCV000328206 pathogenic Cystinosis 2016-10-06 no assertion criteria provided literature only
Natera, Inc. RCV000258029 SCV001463143 pathogenic Cystinosis 2020-09-16 no assertion criteria provided clinical testing

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