NM_006005.3(WFS1):c.1628T>G (p.Leu543Arg) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 6, 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:: RCV002651811.3

Allele description [Variation Report for NM_006005.3(WFS1):c.1628T>G (p.Leu543Arg)]

NM_006005.3(WFS1):c.1628T>G (p.Leu543Arg)

Gene:

WFS1:wolframin ER transmembrane glycoprotein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4p16.1

Genomic location:

Preferred name:

NM_006005.3(WFS1):c.1628T>G (p.Leu543Arg)

HGVS:

NC_000004.12:g.6301423T>G
NG_011700.1:g.36574T>G
NM_001145853.1:c.1628T>G
NM_006005.3:c.1628T>GMANE SELECT
NP_001139325.1:p.Leu543Arg
NP_005996.1:p.Leu543Arg
NP_005996.2:p.Leu543Arg
LRG_1417t1:c.1628T>G
LRG_1417:g.36574T>G
LRG_1417p1:p.Leu543Arg
NC_000004.11:g.6303150T>G
NM_006005.2:c.1628T>G

Protein change:

L543R

Molecular consequence:

NM_001145853.1:c.1628T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006005.3:c.1628T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003525594	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 6, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 12754709, 16151413, 32179840, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003525594

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 6, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

Molecular detection of novel WFS1 mutations in patients with Wolfram syndrome by a DHPLC-based assay.

Colosimo A, Guida V, Rigoli L, Di Bella C, De Luca A, Briuglia S, Stuppia L, Salpietro DC, Dallapiccola B.

Hum Mutat. 2003 Jun;21(6):622-9.

PubMed [citation]

PMID:: 12754709

Mutation analysis of the WFS1 gene in seven Danish Wolfram syndrome families; four new mutations identified.

Hansen L, Eiberg H, Barrett T, Bek T, Kjaersgaard P, Tranebjaerg L, Rosenberg T.

Eur J Hum Genet. 2005 Dec;13(12):1275-84.

PubMed [citation]

PMID:: 16151413

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003525594.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This missense change has been observed in individual(s) with Wolfram syndrome (PMID: 12754709, 16151413, 32179840). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 543 of the WFS1 protein (p.Leu543Arg).

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine