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

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Mar 12, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000004708.14

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:: Nephropathic cystinosis (CTNS)
Synonyms:: Lysosomal cystine transport protein, defect of; Cystinosin, defect of; Abderhalden Lignac Kaufmann disease; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0100151; MedGen: C2931187; Orphanet: 213; Orphanet: 411629; OMIM: 219800

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000024883	OMIM	no assertion criteria provided	Pathogenic (Sep 1, 2001)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000485611	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Pathogenic (Sep 9, 2016)	unknown	clinical testing	PubMed (10) [See all records that cite these PMIDs] 24464559, 15128704, 11565547, 12825071, 12204010, 10556299, 12442267, 21786142, 9792862, 19863563 mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf, Citation Link,
SCV003841896	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 23, 2023)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12204010, 25741868
SCV004031451	Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 3, 2023)	inherited	clinical testing
SCV004212934	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 12, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
Turkish	inherited	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutational Spectrum of the CTNS Gene in Egyptian Patients with Nephropathic Cystinosis.

Soliman NA, Elmonem MA, van den Heuvel L, Abdel Hamid RH, Gamal M, Bongaers I, Marie S, Levtchenko E.

JIMD Rep. 2014;14:87-97. doi: 10.1007/8904_2013_288. Epub 2014 Jan 25.

PubMed [citation]

PMID:: 24464559
PMCID:: PMC4213330

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 (11)

Details of each submission

From OMIM, SCV000024883.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 4 children with nephropathic cystinosis (219800) in the Old Order Amish population in southwestern Ohio, Rupar et al. (2001) identified a G-to-A transition at nucleotide 1354. This transition resulted in a glycine-to-arginine substitution at residue 339 (G339R). It was found in homozygous form in affected children and in heterozygous form in an unaffected sib.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Counsyl, SCV000485611.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From 3billion, SCV003841896.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.004%). Protein truncation variants are a common disease-causing mechanism. Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID: 12204010). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.97; 3Cnet: 0.94). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000004455). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, SCV004031451.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Turkish	not provided	not provided	not provided	clinical testing	not provided

Description

In-Silico PredictorsPP3: Pathogenic Strong

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004212934.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 25, 2024

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