ClinVar Miner

Submissions for variant NM_004937.3(CTNS):c.559_561+24del

dbSNP: rs113994211
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000020627 SCV000221139 likely pathogenic Nephropathic cystinosis 2015-02-15 criteria provided, single submitter literature only
Invitae RCV002513143 SCV000816935 pathogenic Ocular cystinosis; Juvenile nephropathic cystinosis; Inborn genetic diseases 2024-01-04 criteria provided, single submitter clinical testing This variant results in the deletion of part of exon 8 of the CTNS gene. RNA analysis indicates that a similar copy number variant induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs771633120, gnomAD 0.008%). A similar copy number variant has been observed in individual(s) with infantile cystinosis (PMID: 11562417). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as 898–900_x0001_+24del27 . ClinVar contains an entry for this variant (Variation ID: 21442). Studies have shown that a similar copy number variant results in multiple aberrant spliced transcripts and introduces a premature termination codon (PMID: 11562417). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
Laboratory of Cyto-molecular Genetics, Department of Anatomy, All India Institute of Medical Sciences (AIIMS), New Delhi RCV001843459 SCV002102789 likely pathogenic Infantile nephropathic cystinosis 2022-03-07 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002243658 SCV002808694 pathogenic Ocular cystinosis; Juvenile nephropathic cystinosis; Nephropathic cystinosis 2022-03-02 criteria provided, single submitter clinical testing
Baylor Genetics RCV000020627 SCV004212931 pathogenic Nephropathic cystinosis 2023-10-19 criteria provided, single submitter clinical testing
GeneReviews RCV000020627 SCV000041139 pathologic Nephropathic cystinosis 2011-08-11 no assertion criteria provided curation Converted during submission to Pathogenic.
Sydney Genome Diagnostics, Children's Hospital Westmead RCV001328195 SCV001449313 pathogenic Cystinosis 2018-03-12 no assertion criteria provided clinical testing This individual is heterozygous for the c.559_561+24del variant in the CTNS gene. This variant has been previously reported multiple times, as 898-900_24del27, in the literature as a known founder mutation, originating in Brittany, France. This deletion has been shown to abolish the splice donor consensus site of CTNS exon 8, resulting in aberrant transcript splicing (Kalatzis et al J Am Soc Nephrol 2001 (12):2170-2174; Attard et al Hum Mol Genetics 1999 8(13):2507-2514). This variant is considered to be pathogenic according to the ACMG guidelines.

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