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NM_000441.2(SLC26A4):c.2168A>G (p.His723Arg) AND Rare genetic deafness

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 27, 2019
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:
RCV000036477.6

Allele description [Variation Report for NM_000441.2(SLC26A4):c.2168A>G (p.His723Arg)]

NM_000441.2(SLC26A4):c.2168A>G (p.His723Arg)

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.2168A>G (p.His723Arg)
HGVS:
  • NC_000007.14:g.107710132A>G
  • NG_008489.1:g.54498A>G
  • NM_000441.2:c.2168A>GMANE SELECT
  • NP_000432.1:p.His723Arg
  • NC_000007.13:g.107350577A>G
  • NM_000441.1:c.2168A>G
  • O43511:p.His723Arg
  • c.2168A>G
Protein change:
H723R; HIS723ARG
Links:
UniProtKB: O43511#VAR_007449; OMIM: 605646.0011; dbSNP: rs121908362
NCBI 1000 Genomes Browser:
rs121908362
Molecular consequence:
  • NM_000441.2:c.2168A>G - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
loss_of_function_variant [Sequence Ontology: SO:0002054]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000060132Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Aug 27, 2019)
germlineclinical testing

PubMed (15)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Two frequent missense mutations in Pendred syndrome.

Van Hauwe P, Everett LA, Coucke P, Scott DA, Kraft ML, Ris-Stalpers C, Bolder C, Otten B, de Vijlder JJ, Dietrich NL, Ramesh A, Srisailapathy SC, Parving A, Cremers CW, Willems PJ, Smith RJ, Green ED, Van Camp G.

Hum Mol Genet. 1998 Jul;7(7):1099-104.

PubMed [citation]
PMID:
9618166

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
See all PubMed Citations (15)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000060132.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (15)

Description

The p.His723Arg variant in SLC26A4 has been reported in 37 probands with Pendred syndrome (Wu 2005, Van Hauwe 1998, Lee 2008, Asakura 2010, Cho 2006, Dai 2008, Hu 2007, Ishihara 2010, Kim 2009, Park 2003, Reyes 2009, Tsukamoto 2003, Usami 1999, Yoon 2008). Many of these probands were homozygous or compound heterozygous, and the variant has segregated with disease in several families. Furthermore, functional studies revealed that the p.His723Arg variant disrupts the normal cellular localization and ion transport activity of the protein (Yoon 2008, Ishihara 2010). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Pendred syndrome. ACMG/AMP Criteria applied: PM3_VeryStrong, PP1_Strong, PS3_Moderate.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 19, 2024