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NM_004937.3(CTNS):c.544T>C (p.Trp182Arg) AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 5, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002519021.9

Allele description [Variation Report for NM_004937.3(CTNS):c.544T>C (p.Trp182Arg)]

NM_004937.3(CTNS):c.544T>C (p.Trp182Arg)

Genes:
CTNS-AS1:CTNS antisense RNA 1 [Gene - HGNC]
CTNS:cystinosin, lysosomal cystine transporter [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.2
Genomic location:
Preferred name:
NM_004937.3(CTNS):c.544T>C (p.Trp182Arg)
HGVS:
  • NC_000017.11:g.3656569T>C
  • NG_012489.2:g.25102T>C
  • NM_001031681.3:c.544T>C
  • NM_001374492.1:c.544T>C
  • NM_001374493.1:c.103T>C
  • NM_001374494.1:c.103T>C
  • NM_001374495.1:c.103T>C
  • NM_001374496.1:c.103T>C
  • NM_004937.3:c.544T>CMANE SELECT
  • NP_001026851.2:p.Trp182Arg
  • NP_001361421.1:p.Trp182Arg
  • NP_001361422.1:p.Trp35Arg
  • NP_001361423.1:p.Trp35Arg
  • NP_001361424.1:p.Trp35Arg
  • NP_001361425.1:p.Trp35Arg
  • NP_004928.2:p.Trp182Arg
  • NC_000017.10:g.3559863T>C
  • NM_004937.2:c.544T>C
  • O60931:p.Trp182Arg
Protein change:
W182R
Links:
UniProtKB: O60931#VAR_010681; dbSNP: rs764168489
NCBI 1000 Genomes Browser:
rs764168489
Molecular consequence:
  • NM_001031681.3:c.544T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374492.1:c.544T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374493.1:c.103T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374494.1:c.103T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374495.1:c.103T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374496.1:c.103T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004937.3:c.544T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Ocular cystinosis
Synonyms:
Cystinosis, ocular nonnephropathic; Cystinosis, adult, nonnephropathic; Cystinosis, benign, nonnephropathic
Identifiers:
MONDO: MONDO:0009064; MedGen: C2931013; Orphanet: 213; OMIM: 219750
Name:
Juvenile nephropathic cystinosis
Synonyms:
CYSTINOSIS, LATE-ONSET JUVENILE OR ADOLESCENT NEPHROPATHIC TYPE
Identifiers:
MONDO: MONDO:0009066; MedGen: C0268626; Orphanet: 213; Orphanet: 411634; OMIM: 219900
Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002272022Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Oct 5, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

CTNS mutations in an American-based population of cystinosis patients.

Shotelersuk V, Larson D, Anikster Y, McDowell G, Lemons R, Bernardini I, Guo J, Thoene J, Gahl WA.

Am J Hum Genet. 1998 Nov;63(5):1352-62.

PubMed [citation]
PMID:
9792862
PMCID:
PMC1377545

Molecular pathogenesis of cystinosis: effect of CTNS mutations on the transport activity and subcellular localization of cystinosin.

Kalatzis V, Nevo N, Cherqui S, Gasnier B, Antignac C.

Hum Mol Genet. 2004 Jul 1;13(13):1361-71. Epub 2004 May 5.

PubMed [citation]
PMID:
15128704
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV002272022.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 182 of the CTNS protein (p.Trp182Arg). This variant is present in population databases (rs764168489, gnomAD 0.003%). This missense change has been observed in individual(s) with cystinosis (PMID: 9792862). ClinVar contains an entry for this variant (Variation ID: 267308). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CTNS protein function. Experimental studies have shown that this missense change affects CTNS function (PMID: 15128704). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 26, 2024