ClinVar Miner

Submissions for variant NM_004937.3(CTNS):c.1015G>A (p.Gly339Arg) (rs121908127)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000004708 SCV000485611 pathogenic Nephropathic cystinosis 2016-09-09 criteria provided, single submitter clinical testing
Invitae RCV001044380 SCV001208174 pathogenic Ocular cystinosis; Juvenile nephropathic cystinosis; Nephropathic cystinosis 2019-12-12 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 339 of the CTNS protein (p.Gly339Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs121908127, ExAC 0.01%). This variant has been reported to segregate with cystinosis in two families (PMID: 11565547) and it has been reported as homozygous or in combination with another CTNS variant in individuals affected with cystinosis (PMID: 23640116, 12825071, 21786142, 12204010, 11565547). ClinVar contains an entry for this variant (Variation ID: 4455). Experimental studies have shown that this missense change does not alter subcellular localization but abrogates CTNS transporter activity (PMID: 15128704). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV001193377 SCV001362153 pathogenic Cystinosis 2019-09-16 criteria provided, single submitter clinical testing Variant summary: CTNS c.1015G>A (p.Gly339Arg) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 251256 control chromosomes (gnomAD). c.1015G>A has been reported in the literature in multiple compound heterozygote and homozygote individuals affected with Cystinosis (eg- Mason_2003, Rupar_2001). These data indicate that the variant is very likely to be associated with disease. A ClinVar submission (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000004708 SCV000024883 pathogenic Nephropathic cystinosis 2001-09-01 no assertion criteria provided literature only
Natera, Inc. RCV001193377 SCV001463155 pathogenic Cystinosis 2020-09-16 no assertion criteria provided clinical testing

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