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NM_006005.3(WFS1):c.1219C>T (p.His407Tyr) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 11, 2013
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:
RCV000152670.6

Allele description [Variation Report for NM_006005.3(WFS1):c.1219C>T (p.His407Tyr)]

NM_006005.3(WFS1):c.1219C>T (p.His407Tyr)

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.1219C>T (p.His407Tyr)
HGVS:
  • NC_000004.12:g.6301014C>T
  • NG_011700.1:g.36165C>T
  • NM_001145853.1:c.1219C>T
  • NM_006005.3:c.1219C>TMANE SELECT
  • NP_001139325.1:p.His407Tyr
  • NP_005996.2:p.His407Tyr
  • LRG_1417t1:c.1219C>T
  • LRG_1417:g.36165C>T
  • LRG_1417p1:p.His407Tyr
  • NC_000004.11:g.6302741C>T
Protein change:
H407Y
Links:
dbSNP: rs151244358
NCBI 1000 Genomes Browser:
rs151244358
Molecular consequence:
  • NM_001145853.1:c.1219C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006005.3:c.1219C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000202031Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)
Uncertain significance
(Oct 11, 2013)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000202031.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

Variant classified as Uncertain Significance - Favor Benign. The His407Tyr varia nt in WFS1 has not been reported in individuals with hearing loss, but has been identified in 0.04% (2/4406) of African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs151244358). Compu tational analyses (biochemical amino acid properties, conservation, AlignGVGD, P olyPhen2, and SIFT) suggest that the His407Tyr variant may not impact the protei n, though this information is not predictive enough to rule out pathogenicity. I n summary, the clinical significance of this variant cannot be determined with c ertainty; however based upon the computational data, we would lean towards a mor e likely benign role.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: May 16, 2025