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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000060132	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 27, 2019)	germline	clinical testing	PubMed (15) [See all records that cite these PMIDs] 9618166, 10190331, 12676893, 14508505, 15933521, 17443271, 19040761, 18310264, 20826203, 18585793, 17322586, 19565036, 19786220, 20583162, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000060132

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 27, 2019)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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