NM_000441.2(SLC26A4):c.1225C>T (p.Arg409Cys) AND not provided

Clinical significance:Pathogenic (Last evaluated: Jul 10, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000811142.3

Allele description [Variation Report for NM_000441.2(SLC26A4):c.1225C>T (p.Arg409Cys)]

NM_000441.2(SLC26A4):c.1225C>T (p.Arg409Cys)

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.1225C>T (p.Arg409Cys)
HGVS:
  • NC_000007.14:g.107690199C>T
  • NG_008489.1:g.34565C>T
  • NM_000441.2:c.1225C>TMANE SELECT
  • NP_000432.1:p.Arg409Cys
  • NC_000007.13:g.107330644C>T
  • NM_000441.1:c.1225C>T
Protein change:
R409C
Links:
dbSNP: rs147952620
NCBI 1000 Genomes Browser:
rs147952620
Molecular consequence:
  • NM_000441.2:c.1225C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000951393Invitaecriteria provided, single submitter
Pathogenic
(Jul 10, 2019)
germlineclinical testing

PubMed (7)
[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

[Screening of SLC26A4 (PDS) gene mutation in cochlear implant recipients with inner ear malformation].

Chen DY, Chen XW, Jin X, Zuo J, Wei CG, Cao KL, Fang FD.

Zhonghua Yi Xue Za Zhi. 2007 Oct 30;87(40):2820-4. Chinese.

PubMed [citation]
PMID:
18167283

KCNJ10 may not be a contributor to nonsyndromic enlargement of vestibular aqueduct (NSEVA) in Chinese subjects.

Zhao J, Yuan Y, Huang S, Huang B, Cheng J, Kang D, Wang G, Han D, Dai P.

PLoS One. 2014;9(11):e108134. doi: 10.1371/journal.pone.0108134.

PubMed [citation]
PMID:
25372295
PMCID:
PMC4220913
See all PubMed Citations (7)

Details of each submission

From Invitae, SCV000951393.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change replaces arginine with cysteine at codon 409 of the SLC26A4 protein (p.Arg409Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs147952620, ExAC 0.01%). This variant has been reported in several individuals affected with non-syndromic enlargement of vestibular aqueduct and hearing loss (PMID: 18167283, 23185506, 25372295). ClinVar contains an entry for this variant (Variation ID: 371421). Experimental studies have shown that this missense change leads to decreased expression in the cell and retention in the intracellular region (PMID: 23185506). A different missense substitution at this codon (p.Arg408His) has been determined to be pathogenic (PMID: 9618166, 19786220, 24224479). This suggests that the arginine residue is critical for SLC26A4 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 8, 2021

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