Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002527666 | SCV000625760 | pathogenic | Ocular cystinosis; Juvenile nephropathic cystinosis; Inborn genetic diseases | 2024-01-27 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ile69Argfs*5) 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 cystinosis (PMID: 10625078). ClinVar contains an entry for this variant (Variation ID: 455787). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001358753 | SCV001554609 | pathogenic | Cystinosis | 2021-03-30 | criteria provided, single submitter | clinical testing | Variant summary: CTNS c.206_210delTCCTT (p.Ile69ArgfsX5) 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. The variant was absent in 251456 control chromosomes. c.206_210delTCCTT has been reported as a homozygous mutation in at least one individual affected with Cystinosis (e.g. Shotelersuk_1998). These data indicate that the variant may be associated with disease. Fibroblasts from this patient were assessed as having higher levels of intracellular cystine compared to normal controls (e.g. Vitcitsky_2010). One other clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and cited the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV000004703 | SCV004215227 | pathogenic | Nephropathic cystinosis | 2022-06-02 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000004703 | SCV000024878 | pathogenic | Nephropathic cystinosis | 1998-11-01 | no assertion criteria provided | literature only |