NM_147196.3(TMIE):c.274C>T (p.Arg92Trp) AND Autosomal recessive nonsyndromic hearing loss 6

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Feb 7, 2018
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:: RCV000003559.11

Allele description [Variation Report for NM_147196.3(TMIE):c.274C>T (p.Arg92Trp)]

NM_147196.3(TMIE):c.274C>T (p.Arg92Trp)

Gene:

TMIE:transmembrane inner ear [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p21.31

Genomic location:

Preferred name:

NM_147196.3(TMIE):c.274C>T (p.Arg92Trp)

HGVS:

NC_000003.12:g.46709188C>T
NG_011628.1:g.12856C>T
NM_001370524.1:c.115C>T
NM_001370525.1:c.115C>T
NM_147196.3:c.274C>TMANE SELECT
NP_001357453.1:p.Arg39Trp
NP_001357454.1:p.Arg39Trp
NP_671729.2:p.Arg92Trp
NP_671729.2:p.Arg92Trp
NC_000003.11:g.46750678C>T
NM_147196.2:c.274C>T
Q8NEW7:p.Arg92Trp

Protein change:

R39W; ARG92TRP

Links:

UniProtKB: Q8NEW7#VAR_021526; OMIM: 607237.0004; dbSNP: rs28941781

NCBI 1000 Genomes Browser:

rs28941781

Molecular consequence:

NM_001370524.1:c.115C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370525.1:c.115C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_147196.3:c.274C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autosomal recessive nonsyndromic hearing loss 6
Synonyms:: NEUROSENSORY NONSYNDROMIC RECESSIVE DEAFNESS 6; Deafness, autosomal recessive 6
Identifiers:: MONDO: MONDO:0010965; MedGen: C1832992; Orphanet: 90636; OMIM: 600971

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000023717	OMIM	no assertion criteria provided	Pathogenic (Sep 1, 2002)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000916023	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Uncertain significance (Apr 28, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV001527473	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 7, 2018)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000023717

OMIM

no assertion criteria provided

Pathogenic
(Sep 1, 2002)

germline

literature only

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

SCV000916023

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)

Uncertain significance
(Apr 28, 2017)

germline

clinical testing

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

Citation Link,

SCV001527473

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 7, 2018)

unknown

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Mutations in a novel gene, TMIE, are associated with hearing loss linked to the DFNB6 locus.

Naz S, Giguere CM, Kohrman DC, Mitchem KL, Riazuddin S, Morell RJ, Ramesh A, Srisailpathy S, Deshmukh D, Riazuddin S, Griffith AJ, Friedman TB, Smith RJ, Wilcox ER.

Am J Hum Genet. 2002 Sep;71(3):632-6. Epub 2002 Jul 24.

PubMed [citation]

PMID:: 12145746
PMCID:: PMC379198

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

Details of each submission

From OMIM, SCV000023717.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a family (PKDF76) with deafness mapping to the DFNB6 (600971) region, Naz et al. (2002) identified a 274C-T transition in the TMIE gene, resulting in an arg92-to-trp (R92W) mutation.

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

From Illumina Laboratory Services, Illumina, SCV000916023.1

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

Description

The TMIE c.274C>T (p.Arg92Trp) missense variant has been reported in a homozygous state in three siblings from one consanguineous family with autosomal recessive nonsyndromic hearing loss (Naz et al. 2002). The variant was absent from two unaffected siblings. No other genes were screened in this study. The p.Arg92Trp variant was absent from 254 controls but is reported at a frequency of 0.00004 in the European (non-Finnish) population of the Exome Aggregation Consortium. The evidence for this variant is limited. The p.Arg92Trp variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for the recessive form of nonsyndromic hearing loss. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#	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 Baylor Genetics, SCV001527473.1

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

Description

This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].

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

Last Updated: Feb 4, 2024

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