NM_147196.3(TMIE):c.191C>T (p.Ser64Leu) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 11, 2016
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:: RCV000152052.8

Allele description [Variation Report for NM_147196.3(TMIE):c.191C>T (p.Ser64Leu)]

NM_147196.3(TMIE):c.191C>T (p.Ser64Leu)

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.191C>T (p.Ser64Leu)

HGVS:

NC_000003.12:g.46705887C>T
NG_011628.1:g.9555C>T
NM_001370524.1:c.32C>T
NM_001370525.1:c.32C>T
NM_147196.3:c.191C>TMANE SELECT
NP_001357453.1:p.Ser11Leu
NP_001357454.1:p.Ser11Leu
NP_671729.2:p.Ser64Leu
NP_671729.2:p.Ser64Leu
NC_000003.11:g.46747377C>T
NM_147196.2:c.191C>T

Protein change:

S11L

Links:

dbSNP: rs189895472

NCBI 1000 Genomes Browser:

rs189895472

Molecular consequence:

NM_001370524.1:c.32C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370525.1:c.32C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_147196.3:c.191C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000200659	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Sep 11, 2016)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24875298, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000200659

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Sep 11, 2016)

germline

clinical testing

PubMed (2)
[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	not provided	4	4	not provided	not provided	not provided	clinical testing

Citations

PubMed

Targeted next-generation sequencing of deafness genes in hearing-impaired individuals uncovers informative mutations.

Vona B, Müller T, Nanda I, Neuner C, Hofrichter MA, Schröder J, Bartsch O, Läßig A, Keilmann A, Schraven S, Kraus F, Shehata-Dieler W, Haaf T.

Genet Med. 2014 Dec;16(12):945-53. doi: 10.1038/gim.2014.65. Epub 2014 May 29.

PubMed [citation]

PMID:: 24875298
PMCID:: PMC4262760

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000200659.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	not provided	clinical testing	PubMed (2)

Description

Variant classified as Uncertain Significance - Favor Benign. The p.Ser64Leu vari ant in TMIE has been previously reported in the heterozygous state in four indiv iduals with hearing loss; however, an alternate explanation of the hearing loss was identified in two of these individuals (Vona 2014, LMM data). This variant h as been identified across several populations by the Exome Aggregation Consortiu m with a frequency of 0.04% (46/120742) of the total chromosomes (ExAC, http://e xac.broadinstitute.org; dbSNP rs189895472). However, its frequency is not high e nough to rule out a pathogenic role. Computational prediction tools and conserva tion analyses do not provide strong support for or against an impact to the prot ein. In summary, while the clinical significance of the p.Ser64Leu variant is un certain, the identification of the variant in several individuals with an altern ate explanation of the hearing loss suggests it is more likely benign.

#	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		4	not provided	4	not provided

Last Updated: Sep 29, 2024

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