NM_000441.2(SLC26A4):c.1920G>C (p.Trp640Cys) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Jun 12, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000607312.2

Allele description [Variation Report for NM_000441.2(SLC26A4):c.1920G>C (p.Trp640Cys)]

NM_000441.2(SLC26A4):c.1920G>C (p.Trp640Cys)

Gene:
SLC26A4:solute carrier family 26 member 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q22.3
Genomic location:
Preferred name:
NM_000441.2(SLC26A4):c.1920G>C (p.Trp640Cys)
HGVS:
  • NC_000007.14:g.107701943G>C
  • NG_008489.1:g.46309G>C
  • NM_000441.2:c.1920G>CMANE SELECT
  • NP_000432.1:p.Trp640Cys
  • NC_000007.13:g.107342388G>C
  • NM_000441.1:c.1920G>C
Protein change:
W640C
Links:
dbSNP: rs368119540
NCBI 1000 Genomes Browser:
rs368119540
Molecular consequence:
  • NM_000441.2:c.1920G>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

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
SCV000711200Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Uncertain significance
(Jun 12, 2017)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided32not 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, Partners HealthCare Personalized Medicine, SCV000711200.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testing PubMed (1)

Description

Variant classified as Uncertain Significance - Favor Pathogenic. The p.Trp640Cys variant in SLC26A4 has been identified by our laboratory in 2 individual with h earing loss, including 1 individual who carried a 2nd established pathogenic SLC 26A4 allele in trans with the p.Trp640Cys allele (this individual) and 1 individ ual with hearing loss and EVA, however a second SLC26A4 variant was not detected (LMM unpublished data). The variant has also been identified in 3/111444 Europe an chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadin stitute.org; dbSNP rs769086004); however, this frequency is not high enough to r ule out a pathogenic role. Computational prediction tools and conservation analy sis suggest that the variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, while there is som e suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PP3; PM2; PM3 (Richards 2015).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided3not provided2not provided

Last Updated: Jul 7, 2021

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