NM_000441.2(SLC26A4):c.225C>G (p.Leu75=) AND Pendred syndrome

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Nov 4, 2021
Review status:: criteria provided, conflicting classifications

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:: RCV000666650.9

Allele description [Variation Report for NM_000441.2(SLC26A4):c.225C>G (p.Leu75=)]

NM_000441.2(SLC26A4):c.225C>G (p.Leu75=)

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.225C>G (p.Leu75=)

HGVS:

NC_000007.14:g.107663356C>G
NG_008489.1:g.7722C>G
NM_000441.2:c.225C>GMANE SELECT
NP_000432.1:p.Leu75=
NC_000007.13:g.107303801C>G
NM_000441.1:c.225C>G

Links:

dbSNP: rs187447337

NCBI 1000 Genomes Browser:

rs187447337

Molecular consequence:

NM_000441.2:c.225C>G - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:: Pendred syndrome (PDS)
Synonyms:: DEAFNESS WITH GOITER; HYPOTHYROIDISM, CONGENITAL, DUE TO DYSHORMONOGENESIS, 2B; THYROID DYSHORMONOGENESIS 2B; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010134; MedGen: C0271829; Orphanet: 705; OMIM: 274600

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001455794	Natera, Inc.	no assertion criteria provided	Likely benign (Sep 16, 2020)	germline	clinical testing
SCV001652721	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (May 18, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002060189	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2021))	Uncertain significance (Nov 4, 2021)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 25788563, 15355436, 23185506, 33152970 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001455794

Natera, Inc.

no assertion criteria provided

Likely benign
(Sep 16, 2020)

germline

clinical testing

SCV001652721

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(May 18, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002060189

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2021))

Uncertain significance
(Nov 4, 2021)

unknown

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Deafness gene variations in a 1120 nonsyndromic hearing loss cohort: molecular epidemiology and deafness mutation spectrum of patients in Japan.

Nishio SY, Usami S.

Ann Otol Rhinol Laryngol. 2015 May;124 Suppl 1:49S-60S. doi: 10.1177/0003489415575059. Epub 2015 Mar 18.

PubMed [citation]

PMID:: 25788563

See all PubMed Citations (5)

Details of each submission

From Natera, Inc., SCV001455794.1

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

#	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 Genome-Nilou Lab, SCV001652721.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Myriad Genetics, Inc., SCV002060189.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

NM_000441.1(SLC26A4):c.225C>G(L75=) is a silent variant classified as a variant of uncertain significance in the context of Pendred syndrome. L75= has been observed in cases with relevant disease (PMID: 23185506, 25788563, 15355436, 33152970). Functional assessments of this variant are not available in the literature. L75= has been observed in population frequency databases (gnomAD: EAS 0.09%). In summary, there is insufficient evidence to classify NM_000441.1(SLC26A4):c.225C>G(L75=) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening.

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

Last Updated: May 26, 2024

ClinVar

Relating variation to medicine