NM_004937.3(CTNS):c.1015G>A (p.Gly339Arg) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 7, 2024
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:
RCV002512767.10

Allele description [Variation Report for NM_004937.3(CTNS):c.1015G>A (p.Gly339Arg)]

NM_004937.3(CTNS):c.1015G>A (p.Gly339Arg)

Gene:
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.1015G>A (p.Gly339Arg)
HGVS:
  • NC_000017.11:g.3660280G>A
  • NG_012489.2:g.28813G>A
  • NM_001031681.3:c.1015G>A
  • NM_001374492.1:c.1015G>A
  • NM_001374493.1:c.574G>A
  • NM_001374494.1:c.574G>A
  • NM_001374495.1:c.574G>A
  • NM_001374496.1:c.574G>A
  • NM_004937.3:c.1015G>AMANE SELECT
  • NP_001026851.2:p.Gly339Arg
  • NP_001361421.1:p.Gly339Arg
  • NP_001361422.1:p.Gly192Arg
  • NP_001361423.1:p.Gly192Arg
  • NP_001361424.1:p.Gly192Arg
  • NP_001361425.1:p.Gly192Arg
  • NP_004928.2:p.Gly339Arg
  • NC_000017.10:g.3563574G>A
  • NM_001031681.2:c.1015G>A
  • NM_004937.2:c.1015G>A
  • O60931:p.Gly339Arg
Protein change:
G192R; GLY339ARG
Links:
UniProtKB: O60931#VAR_010695; OMIM: 606272.0015; dbSNP: rs121908127
NCBI 1000 Genomes Browser:
rs121908127
Molecular consequence:
  • NM_001031681.3:c.1015G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374492.1:c.1015G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374493.1:c.574G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374494.1:c.574G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374495.1:c.574G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374496.1:c.574G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004937.3:c.1015G>A - 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
SCV001208174Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 7, 2024) 		germlineclinical testing

PubMed (7)
[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

A G339R mutation in the CTNS gene is a common cause of nephropathic cystinosis in the south western Ontario Amish Mennonite population.

Rupar CA, Matsell D, Surry S, Siu V.

J Med Genet. 2001 Sep;38(9):615-6. No abstract available.

PubMed [citation]
PMID:
11565547
PMCID:
PMC1734937

Analysis of the CTNS gene in patients of German and Swiss origin with nephropathic cystinosis.

Kiehntopf M, Schickel J, Gönne Bv, Koch HG, Superti-Furga A, Steinmann B, Deufel T, Harms E.

Hum Mutat. 2002 Sep;20(3):237.

PubMed [citation]
PMID:
12204010
See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001208174.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 339 of the CTNS protein (p.Gly339Arg). This variant is present in population databases (rs121908127, gnomAD 0.005%). This missense change has been observed in individuals with cystinosis (PMID: 11565547, 12204010, 12825071, 21786142, 23640116). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4455). 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 with a positive predictive value of 80%. Experimental studies have shown that this missense change affects CTNS function (PMID: 15128704). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 13, 2024