Submissions for variant NM_004937.3(CTNS):c.611ACG[1] (p.Asp205del)

dbSNP: rs760256854

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000169014	SCV000220155	likely pathogenic	Nephropathic cystinosis	2014-03-12	criteria provided, single submitter	literature only
Labcorp Genetics (formerly Invitae), Labcorp	RCV002516526	SCV002237871	pathogenic	Ocular cystinosis; Juvenile nephropathic cystinosis; Inborn genetic diseases	2024-10-29	criteria provided, single submitter	clinical testing	This variant, c.614_616del, results in the deletion of 1 amino acid(s) of the CTNS protein (p.Asp205del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs760256854, gnomAD 0.01%). This variant has been observed in individual(s) with cystinosis (PMID: 9792862, 10556299). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 188718). Algorithms developed to predict the effect of variants on gene product structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects CTNS function (PMID: 15128704). This variant disrupts a region of the CTNS protein in which other variant(s) (p.Asp205Asn) have been determined to be pathogenic (PMID: 9792862, 22528245, 28983406). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000258027	SCV002511700	pathogenic	Cystinosis	2022-04-25	criteria provided, single submitter	clinical testing	Variant summary: CTNS c.614_616delACG (p.Asp205del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 1.2e-05 in 251348 control chromosomes. c.614_616delACG has been reported in the literature in individuals affected with Cystinosis in homozygous and compound heterozygous states. These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics	RCV000169014	SCV004212933	pathogenic	Nephropathic cystinosis	2024-01-23	criteria provided, single submitter	clinical testing
GeneReviews	RCV000258027	SCV000328211	not provided	Cystinosis		no assertion provided	literature only