NM_000441.2(SLC26A4):c.554G>C (p.Arg185Thr) AND Rare genetic deafness

Clinical significance:Pathogenic (Last evaluated: Jan 4, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000214962.1

Allele description [Variation Report for NM_000441.2(SLC26A4):c.554G>C (p.Arg185Thr)]

NM_000441.2(SLC26A4):c.554G>C (p.Arg185Thr)

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.554G>C (p.Arg185Thr)
Other names:
NM_000441.1(SLC26A4):c.554G>C(p.Arg185Thr)
HGVS:
  • NC_000007.14:g.107674302G>C
  • NG_008489.1:g.18668G>C
  • NM_000441.2:c.554G>CMANE SELECT
  • NP_000432.1:p.Arg185Thr
  • NC_000007.13:g.107314747G>C
  • NM_000441.1:c.554G>C
  • NM_000441.2(SLC26A4):c.554G>CMANE SELECT
  • O43511:p.Arg185Thr
Protein change:
R185T
Links:
UniProtKB: O43511#VAR_064991; dbSNP: rs542620119
NCBI 1000 Genomes Browser:
rs542620119
Molecular consequence:
  • NM_000441.2:c.554G>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Rare genetic deafness
Identifiers:
MedGen: CN826980; Orphanet: 96210

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000271454Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Pathogenic
(Jan 4, 2016)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

Spectrum and frequency of SLC26A4 mutations among Czech patients with early hearing loss with and without Enlarged Vestibular Aqueduct (EVA).

Pourová R, Janousek P, Jurovcík M, Dvoráková M, Malíková M, Rasková D, Bendová O, Leonardi E, Murgia A, Kabelka Z, Astl J, Seeman P.

Ann Hum Genet. 2010 Jul;74(4):299-307. doi: 10.1111/j.1469-1809.2010.00581.x.

PubMed [citation]
PMID:
20597900

Use of SLC26A4 mutation testing for unilateral enlargement of the vestibular aqueduct.

Chattaraj P, Reimold FR, Muskett JA, Shmukler BE, Chien WW, Madeo AC, Pryor SP, Zalewski CK, Butman JA, Brewer CC, Kenna MA, Alper SL, Griffith AJ.

JAMA Otolaryngol Head Neck Surg. 2013 Sep;139(9):907-13. doi: 10.1001/jamaoto.2013.4185. Erratum in: JAMA Otolaryngol Head Neck Surg. 2014 Dec;140(12):1212.

PubMed [citation]
PMID:
24051746
See all PubMed Citations (4)

Details of each submission

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000271454.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (4)

Description

The p.Arg185Thr variant in SLC26A4 has been previously reported in three individ uals with hearing loss and enlarged vestibular aqueducts, including one individu al who was compound heterozygous for a second pathogenic variant in the SLC26A4 gene (Chattaraj 2013, Cirello 2012, Pourova 2010). This variant has been identif ied in 12/66734 (0.02%) of European chromosomes by the Exome Aggregation Consort ium (ExAC, http://exac.broadinstitute.org; dbSNP rs542620119); however, this fre quency is low enough to be consistent with a recessive carrier frequency. In vit ro functional studies reveal that the variant results in abnormal cellular local ization of the protein and significant reduction in its normal functional activi ty (Cirello 2012, Chattaraj 2013), supporting a deleterious effect for this vari ant. In addition, computational tools and conservation analyses predict that the p.Arg185Thr variant may impact the protein. In summary, this variant meets our criteria to be classified as pathogenic.

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

Last Updated: Oct 16, 2021

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