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NM_004937.3(CTNS):c.681+1G>A AND Cystinosis

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Jan 2, 2022
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:
RCV001824939.10

Allele description [Variation Report for NM_004937.3(CTNS):c.681+1G>A]

NM_004937.3(CTNS):c.681+1G>A

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.681+1G>A
HGVS:
  • NC_000017.11:g.3656796G>A
  • NG_012489.2:g.25329G>A
  • NM_001031681.3:c.681+1G>A
  • NM_001374492.1:c.681+1G>A
  • NM_001374493.1:c.240+1G>A
  • NM_001374494.1:c.240+1G>A
  • NM_001374495.1:c.240+1G>A
  • NM_001374496.1:c.240+1G>A
  • NM_004937.3:c.681+1G>AMANE SELECT
  • NC_000017.10:g.3560090G>A
  • NM_004937.2:c.681+1G>A
Links:
dbSNP: rs749317721
NCBI 1000 Genomes Browser:
rs749317721
Molecular consequence:
  • NM_001031681.3:c.681+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001374492.1:c.681+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001374493.1:c.240+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001374494.1:c.240+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001374495.1:c.240+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001374496.1:c.240+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_004937.3:c.681+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Cystinosis
Synonyms:
Cystine diathesis; Cystine disease; Cystine storage disease; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0016239; MedGen: C4316899

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002074196Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Jan 2, 2022) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV002093234Natera, Inc.
no assertion criteria provided
Pathogenic
(Sep 24, 2021) 		germlineclinical testing

Help

Summary from all submissions

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

Citations

PubMed

Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin.

Attard M, Jean G, Forestier L, Cherqui S, van't Hoff W, Broyer M, Antignac C, Town M.

Hum Mol Genet. 1999 Dec;8(13):2507-14.

PubMed [citation]
PMID:
10556299

Mutational spectrum of the CTNS gene in Italy.

Mason S, Pepe G, Dall'Amico R, Tartaglia S, Casciani S, Greco M, Bencivenga P, Murer L, Rizzoni G, Tenconi R, Clementi M.

Eur J Hum Genet. 2003 Jul;11(7):503-8.

PubMed [citation]
PMID:
12825071

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002074196.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: CTNS c.681+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes the canonical 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8e-06 in 250784 control chromosomes. c.681+1G>A has been reported in the literature in multiple individuals affected with Cystinosis (example, Attard_1999, Mason_2003). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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

From Natera, Inc., SCV002093234.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 24, 2024