U.S. flag

An official website of the United States government

NM_004937.3(CTNS):c.635C>T (p.Ala212Val) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 21, 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:
RCV002543797.9

Allele description [Variation Report for NM_004937.3(CTNS):c.635C>T (p.Ala212Val)]

NM_004937.3(CTNS):c.635C>T (p.Ala212Val)

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.635C>T (p.Ala212Val)
HGVS:
  • NC_000017.11:g.3656749C>T
  • NG_012489.2:g.25282C>T
  • NM_001031681.3:c.635C>T
  • NM_001374492.1:c.635C>T
  • NM_001374493.1:c.194C>T
  • NM_001374494.1:c.194C>T
  • NM_001374495.1:c.194C>T
  • NM_001374496.1:c.194C>T
  • NM_004937.3:c.635C>TMANE SELECT
  • NP_001026851.2:p.Ala212Val
  • NP_001361421.1:p.Ala212Val
  • NP_001361422.1:p.Ala65Val
  • NP_001361423.1:p.Ala65Val
  • NP_001361424.1:p.Ala65Val
  • NP_001361425.1:p.Ala65Val
  • NP_004928.2:p.Ala212Val
  • NC_000017.10:g.3560043C>T
  • NG_012489.1:g.25282C>T
Protein change:
A212V
Links:
dbSNP: rs776658046
NCBI 1000 Genomes Browser:
rs776658046
Molecular consequence:
  • NM_001031681.3:c.635C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374492.1:c.635C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374493.1:c.194C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374494.1:c.194C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374495.1:c.194C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374496.1:c.194C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004937.3:c.635C>T - 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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001511029Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jan 21, 2024)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

A case of ocular cystinosis associated with two potentially severe CTNS mutations.

Browning AC, Figueiredo GS, Baylis O, Montgomery E, Beesley C, Molinari E, Figueiredo FC, Sayer JA.

Ophthalmic Genet. 2019 Apr;40(2):157-160. doi: 10.1080/13816810.2019.1592198. Epub 2019 Apr 6.

PubMed [citation]
PMID:
30957593

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001511029.4

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

Description

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 212 of the CTNS protein (p.Ala212Val). This variant is present in population databases (rs776658046, gnomAD 0.006%). This missense change has been observed in individual(s) with cystinosis (PMID: 30957593). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1020638). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CTNS protein function. This variant disrupts the p.Ala212 amino acid residue in CTNS. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: Jul 15, 2024