ClinVar Miner

Submissions for variant NM_004937.3(CTNS):c.559_561+24del (rs113994211)

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Total submissions: 3
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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 RCV000689292 SCV000816935 pathogenic Ocular cystinosis; Juvenile nephropathic cystinosis; Nephropathic cystinosis 2018-07-24 criteria provided, single submitter clinical testing This sequence change removes the last 2 nucleotides of exon 8, and affects the donor splice site in intron 8 of the CTNS gene. It is expected to disrupt RNA splicing and/or create a premature translational stop signal, and likely results in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported as homozygous or in combination with another CTNS variant in individuals affected with cystinosis (PMID:  11562417) and in at least one of these individuals this variant has been observed on the opposite chromosome (in trans) from another pathogenic variant (PMID: 10556299). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant is also known as 898–900_x0001_+24del27 in the literature. ClinVar contains an entry for this variant (Variation ID: 21442). Experimental studies have shown that this deletion change causes aberrant splicing (PMID: 11562417). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CTNS are known to be pathogenic (PMID: 9537412, 27102039). For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000020627 SCV000041139 pathologic Nephropathic cystinosis 2011-08-11 no assertion criteria provided curation Converted during submission to Pathogenic.

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