NM_000441.2(SLC26A4):c.2170G>A (p.Asp724Asn) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 29, 2023
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:: RCV003558498.2

Allele description [Variation Report for NM_000441.2(SLC26A4):c.2170G>A (p.Asp724Asn)]

NM_000441.2(SLC26A4):c.2170G>A (p.Asp724Asn)

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.2170G>A (p.Asp724Asn)

HGVS:

NC_000007.14:g.107710134G>A
NG_008489.1:g.54500G>A
NM_000441.2:c.2170G>AMANE SELECT
NP_000432.1:p.Asp724Asn
NC_000007.13:g.107350579G>A
NM_000441.1:c.2170G>A

Protein change:

D724N

Links:

dbSNP: rs994170964

NCBI 1000 Genomes Browser:

rs994170964

Molecular consequence:

NM_000441.2:c.2170G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004295507	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 29, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 15355436, 14679580, 15811013, 19017801, 24224479, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004295507

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 29, 2023)

germline

clinical testing

PubMed (6)
[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

Screening of SLC26A4 (PDS) gene in Pendred's syndrome: a large spectrum of mutations in France and phenotypic heterogeneity.

Blons H, Feldmann D, Duval V, Messaz O, Denoyelle F, Loundon N, Sergout-Allaoui A, Houang M, Duriez F, Lacombe D, Delobel B, Leman J, Catros H, Journel H, Drouin-Garraud V, Obstoy MF, Toutain A, Oden S, Toublanc JE, Couderc R, Petit C, Garabédian EN, et al.

Clin Genet. 2004 Oct;66(4):333-40.

PubMed [citation]

PMID:: 15355436

Pendred syndrome and DFNB4-mutation screening of SLC26A4 by denaturing high-performance liquid chromatography and the identification of eleven novel mutations.

Prasad S, Kölln KA, Cucci RA, Trembath RC, Van Camp G, Smith RJ.

Am J Med Genet A. 2004 Jan 1;124A(1):1-9.

PubMed [citation]

PMID:: 14679580

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004295507.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 724 of the SLC26A4 protein (p.Asp724Asn). This variant is present in population databases (no rsID available, gnomAD 0.03%). This missense change has been observed in individual(s) with Pendred syndrome (PMID: 15355436). ClinVar contains an entry for this variant (Variation ID: 553188). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SLC26A4 protein function with a positive predictive value of 95%. This variant disrupts the p.Asp724 amino acid residue in SLC26A4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 14679580, 15811013, 19017801, 24224479). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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: Sep 29, 2024

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