Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002532045 | SCV003443723 | likely pathogenic | Ocular cystinosis; Juvenile nephropathic cystinosis; Inborn genetic diseases | 2024-10-30 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 5 of the CTNS gene. It does not directly change the encoded amino acid sequence of the CTNS protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or altered protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with cystinosis (PMID: 12442267). This variant is also known as 564+1del4. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exons 4 and 5 , and produces a non-functional protein and/or introduces a premature termination codon (PMID: 12442267). This variant disrupts the c.225+5 nucleotide in the CTNS gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 11708862). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Baylor Genetics | RCV000665684 | SCV004212939 | likely pathogenic | Nephropathic cystinosis | 2024-03-18 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000665684 | SCV000789843 | uncertain significance | Nephropathic cystinosis | 2017-02-24 | flagged submission | clinical testing |