NM_004937.3(CTNS):c.833T>C (p.Leu278Pro) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 30, 2021
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:: RCV002537158.9

Allele description [Variation Report for NM_004937.3(CTNS):c.833T>C (p.Leu278Pro)]

NM_004937.3(CTNS):c.833T>C (p.Leu278Pro)

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.833T>C (p.Leu278Pro)

HGVS:

NC_000017.11:g.3658156T>C
NG_012489.2:g.26689T>C
NM_001031681.3:c.833T>C
NM_001374492.1:c.833T>C
NM_001374493.1:c.392T>C
NM_001374494.1:c.392T>C
NM_001374495.1:c.392T>C
NM_001374496.1:c.392T>C
NM_004937.3:c.833T>CMANE SELECT
NP_001026851.2:p.Leu278Pro
NP_001361421.1:p.Leu278Pro
NP_001361422.1:p.Leu131Pro
NP_001361423.1:p.Leu131Pro
NP_001361424.1:p.Leu131Pro
NP_001361425.1:p.Leu131Pro
NP_004928.2:p.Leu278Pro
NC_000017.10:g.3561450T>C
NM_004937.2:c.833T>C

Protein change:

L131P

Links:

dbSNP: rs1314998853

NCBI 1000 Genomes Browser:

rs1314998853

Molecular consequence:

NM_001031681.3:c.833T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374492.1:c.833T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374493.1:c.392T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374494.1:c.392T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374495.1:c.392T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374496.1:c.392T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004937.3:c.833T>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
SCV000943246	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 30, 2021)	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

SCV000943246

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 30, 2021)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000943246.3

#	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 leucine with proline at codon 278 of the CTNS protein (p.Leu278Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with CTNS-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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: Nov 24, 2024

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