Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000608726 | SCV000712077 | pathogenic | Cystinosis | 2016-05-15 | criteria provided, single submitter | clinical testing | The p.Tyr290X variant in CTNS has been reported in 1 patient with nephropathic c ystinosis in the homozygous state (Shotelersuk 1998) and was absent from large p opulation studies. This nonsense variant leads to a premature termination codon at position 290, which is predicted to lead to a truncated or absent protein. Bi allelic loss of function of the CTNS gene is associated with nephropathic cystin osis. In summary, the p.Tyr290X variant meets our criteria to be classified as p athogenic for nephropathic cystinosis in an autosomal recessive manner based upo n its predicted functional impact, homozygous identification in an affected indi vidual, and absence from controls. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000608726 | SCV002051281 | likely pathogenic | Cystinosis | 2021-12-20 | criteria provided, single submitter | clinical testing | Variant summary: CTNS c.870C>G (p.Tyr290X) 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 250904 control chromosomes (gnomAD). c.870C>G has been reported in at least one homozygous individual affected with Cystinosis (example: 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. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV003465352 | SCV004215223 | pathogenic | Nephropathic cystinosis | 2024-01-20 | criteria provided, single submitter | clinical testing |