NM_004937.3(CTNS):c.976T>C (p.Trp326Arg) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 15, 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:: RCV002943197.1

Allele description

NM_004937.3(CTNS):c.976T>C (p.Trp326Arg)

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.976T>C (p.Trp326Arg)

HGVS:

NC_000017.11:g.3660241T>C
NG_012489.2:g.28774T>C
NM_001031681.3:c.976T>C
NM_001374492.1:c.976T>C
NM_001374493.1:c.535T>C
NM_001374494.1:c.535T>C
NM_001374495.1:c.535T>C
NM_001374496.1:c.535T>C
NM_004937.3:c.976T>CMANE SELECT
NP_001026851.2:p.Trp326Arg
NP_001361421.1:p.Trp326Arg
NP_001361422.1:p.Trp179Arg
NP_001361423.1:p.Trp179Arg
NP_001361424.1:p.Trp179Arg
NP_001361425.1:p.Trp179Arg
NP_004928.2:p.Trp326Arg
NC_000017.10:g.3563535T>C

Protein change:

W179R

Molecular consequence:

NM_001031681.3:c.976T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374492.1:c.976T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374493.1:c.535T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374494.1:c.535T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374495.1:c.535T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374496.1:c.535T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004937.3:c.976T>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003274276	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 15, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003274276

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 15, 2022)

germline

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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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, SCV003274276.1

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

Description

This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 326 of the CTNS protein (p.Trp326Arg). This variant is present in population databases (rs372665052, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with CTNS-related conditions. 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Feb 13, 2023

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