NM_000441.2(SLC26A4):c.916dup (p.Val306fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 25, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000812506.8

Allele description [Variation Report for NM_000441.2(SLC26A4):c.916dup (p.Val306fs)]

NM_000441.2(SLC26A4):c.916dup (p.Val306fs)

Gene:

SLC26A4:solute carrier family 26 member 4 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

7q22.3

Genomic location:

Preferred name:

NM_000441.2(SLC26A4):c.916dup (p.Val306fs)

HGVS:

NC_000007.14:g.107683352dup
NG_008489.1:g.27718dup
NM_000441.2:c.916dupMANE SELECT
NP_000432.1:p.Val306fs
NC_000007.13:g.107323796_107323797insG
NC_000007.13:g.107323797dup
NM_000441.1:c.916dupG
NM_000441.2:c.916dupGMANE SELECT

Protein change:

V306fs

Links:

dbSNP: rs768245266

NCBI 1000 Genomes Browser:

rs768245266

Molecular consequence:

NM_000441.2:c.916dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000952821	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 25, 2024)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 16283880, 25394566, 26445815, 14715652, 17718863, 21366435, 26252218, 28492532
SCV001167878	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 22, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000952821

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 25, 2024)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

SCV001167878

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jun 22, 2020)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Assessment of the genetic causes of recessive childhood non-syndromic deafness in the UK - implications for genetic testing.

Hutchin T, Coy NN, Conlon H, Telford E, Bromelow K, Blaydon D, Taylor G, Coghill E, Brown S, Trembath R, Liu XZ, Bitner-Glindzicz M, Mueller R.

Clin Genet. 2005 Dec;68(6):506-12.

PubMed [citation]

PMID:: 16283880

Evaluation of genotype-phenotype relationships in patients referred for endocrine assessment in suspected Pendred syndrome.

Soh LM, Druce M, Grossman AB, Differ AM, Rajput L, Bitner-Glindzicz M, Korbonits M.

Eur J Endocrinol. 2015 Feb;172(2):217-26. doi: 10.1530/EJE-14-0679. Epub 2014 Nov 13.

PubMed [citation]

PMID:: 25394566

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000952821.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change creates a premature translational stop signal (p.Val306Glyfs*24) in the SLC26A4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC26A4 are known to be pathogenic (PMID: 16283880, 25394566, 26252218, 26445815). This variant is present in population databases (rs768245266, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with non-syndromic hearing loss and Pendred syndrome (PMID: 14715652, 17718863, 21366435, 26252218). This variant is also known as 916_917insG and 916insG. ClinVar contains an entry for this variant (Variation ID: 370192). 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

From GeneDx, SCV001167878.2

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

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Published functional studies demonstrate a damaging effect on iodide transport (Gillam et al., 2004); This variant is associated with the following publications: (PMID: 30275481, 30896630, 31827275, 31581539, 30842343, 26252218, 14715652, 27240500, 20483489, 23302201, 17718863)

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

Last Updated: Sep 29, 2024

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