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NM_000441.2(SLC26A4):c.2162C>T (p.Thr721Met) AND Rare genetic deafness

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 29, 2016
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:
RCV000154350.5

Allele description [Variation Report for NM_000441.2(SLC26A4):c.2162C>T (p.Thr721Met)]

NM_000441.2(SLC26A4):c.2162C>T (p.Thr721Met)

Genes:
LOC123956210:Sharpr-MPRA regulatory region 3291 [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.2162C>T (p.Thr721Met)
HGVS:
  • NC_000007.14:g.107710126C>T
  • NG_008489.1:g.54492C>T
  • NM_000441.2:c.2162C>TMANE SELECT
  • NP_000432.1:p.Thr721Met
  • NC_000007.13:g.107350571C>T
  • NM_000441.1:c.2162C>T
  • O43511:p.Thr721Met
Protein change:
T721M; THR721MET
Links:
UniProtKB: O43511#VAR_007448; OMIM: 605646.0012; dbSNP: rs121908363
NCBI 1000 Genomes Browser:
rs121908363
Molecular consequence:
  • NM_000441.2:c.2162C>T - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
loss_of_function_variant [Sequence Ontology: SO:0002054]
Observations:
2

Condition(s)

Name:
Rare genetic deafness
Identifiers:
MedGen: C5680250; Orphanet: 96210

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000204013Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Pathogenic
(Mar 29, 2016) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided22not providednot providednot providedclinical testing

Citations

PubMed

Non-syndromic hearing loss associated with enlarged vestibular aqueduct is caused by PDS mutations.

Usami S, Abe S, Weston MD, Shinkawa H, Van Camp G, Kimberling WJ.

Hum Genet. 1999 Feb;104(2):188-92.

PubMed [citation]
PMID:
10190331

Salicylate restores transport function and anion exchanger activity of missense pendrin mutations.

Ishihara K, Okuyama S, Kumano S, Iida K, Hamana H, Murakoshi M, Kobayashi T, Usami S, Ikeda K, Haga Y, Tsumoto K, Nakamura H, Hirasawa N, Wada H.

Hear Res. 2010 Dec 1;270(1-2):110-8. doi: 10.1016/j.heares.2010.08.015. Epub 2010 Sep 6.

PubMed [citation]
PMID:
20826203
See all PubMed Citations (6)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000204013.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (6)

Description

The p.Thr721Met variant in SLC26A4 has been reported in at least 7 individuals f rom 5 families with hearing loss and enlarged vestibular aqueduct (EVA) or Pendr ed Syndrome (Chen 2011, Ishihara 2010, Kahrizi 2009, Lopez-Bigas 2001, Usami 199 9). Individuals were either homozygous (2 families) or heterozygous with anoth er pathogenic variant (3 families). Compound heterozygous variants were confir med to be in trans in at least one family. In addition, a study showed that the Thr721Met variant impacts protein function (Ishihara 2010). This variant has b een identified in 5/11486 Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs121908363); however, this freque ncy is low enough to be consistent with a recessive carrier frequency. In summa ry, this variant meets our criteria to be classified as pathogenic for autosomal recessive hearing loss with EVA or Pendred syndrome.

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

Last Updated: Sep 29, 2024