NM_000441.2(SLC26A4):c.2186T>C (p.Leu729Pro) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 17, 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:: RCV001226428.6

Allele description [Variation Report for NM_000441.2(SLC26A4):c.2186T>C (p.Leu729Pro)]

NM_000441.2(SLC26A4):c.2186T>C (p.Leu729Pro)

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.2186T>C (p.Leu729Pro)

HGVS:

NC_000007.14:g.107710150T>C
NG_008489.1:g.54516T>C
NM_000441.2:c.2186T>CMANE SELECT
NP_000432.1:p.Leu729Pro
NC_000007.13:g.107350595T>C
NM_000441.1:c.2186T>C

Protein change:

L729P

Links:

dbSNP: rs1045933779

NCBI 1000 Genomes Browser:

rs1045933779

Molecular consequence:

NM_000441.2:c.2186T>C - 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
SCV001398741	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 17, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20146813, 23336812, 23401162, 25394566, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001398741

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 17, 2023)

germline

clinical testing

PubMed (5)
[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

High-throughput detection of mutations responsible for childhood hearing loss using resequencing microarrays.

Kothiyal P, Cox S, Ebert J, Husami A, Kenna MA, Greinwald JH, Aronow BJ, Rehm HL.

BMC Biotechnol. 2010 Feb 10;10:10. doi: 10.1186/1472-6750-10-10.

PubMed [citation]

PMID:: 20146813
PMCID:: PMC2841091

SLC26A4 mutation frequency and spectrum in 109 Danish Pendred syndrome/DFNB4 probands and a report of nine novel mutations.

Rendtorff ND, Schrijver I, Lodahl M, Rodriguez-Paris J, Johnsen T, Hansén EC, Nickelsen LA, Tümer Z, Fagerheim T, Wetke R, Tranebjaerg L.

Clin Genet. 2013 Oct;84(4):388-91. doi: 10.1111/cge.12074. Epub 2013 Jan 22. No abstract available.

PubMed [citation]

PMID:: 23336812

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001398741.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SLC26A4 protein function. ClinVar contains an entry for this variant (Variation ID: 552468). This missense change has been observed in individuals with SLC26A4-related conditions (PMID: 20146813, 23336812, 23401162, 25394566). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 729 of the SLC26A4 protein (p.Leu729Pro).

#	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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