NM_153700.2(STRC):c.4402C>T (p.Arg1468Ter) AND Rare genetic deafness

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 5, 2017
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:: RCV000156556.6

Allele description [Variation Report for NM_153700.2(STRC):c.4402C>T (p.Arg1468Ter)]

NM_153700.2(STRC):c.4402C>T (p.Arg1468Ter)

Gene:

STRC:stereocilin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q15.3

Genomic location:

Preferred name:

NM_153700.2(STRC):c.4402C>T (p.Arg1468Ter)

HGVS:

NC_000015.10:g.43603385G>A
NG_011636.1:g.20416C>T
NM_153700.2:c.4402C>TMANE SELECT
NP_714544.1:p.Arg1468Ter
NC_000015.9:g.43895583G>A
p.Arg1468X

Protein change:

R1468*

Links:

dbSNP: rs377480477

NCBI 1000 Genomes Browser:

rs377480477

Molecular consequence:

NM_153700.2:c.4402C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Rare genetic deafness
Identifiers:: MedGen: C5680250; Orphanet: 96210

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000206275	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Jul 5, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25157971, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000206275

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Jul 5, 2017)

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	2	2	not provided	not provided	not provided	clinical testing

Citations

PubMed

Comprehensive diagnostic testing for stereocilin: an approach for analyzing medically important genes with high homology.

Mandelker D, Amr SS, Pugh T, Gowrisankar S, Shakhbatyan R, Duffy E, Bowser M, Harrison B, Lafferty K, Mahanta L, Rehm HL, Funke BH.

J Mol Diagn. 2014 Nov;16(6):639-47. doi: 10.1016/j.jmoldx.2014.06.003. Epub 2014 Aug 23.

PubMed [citation]

PMID:: 25157971

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, SCV000206275.5

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

Description

The p.Arg1468X variant in STRC has been identified by our laboratory in 1 Caucas ian individual with hearing loss who carried a second, pathogenic variant on the other allele. It has also been identified in 18/126662 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs377480477). Although this variant has been seen in the general population, it s frequency is low enough to be consistent with a recessive carrier frequency. T his nonsense variant leads to a premature termination codon at position 1468, wh ich is predicted to lead to a truncated or absent protein. In summary, the p.Arg 1468X variant meets criteria to be classified as pathogenic for hearing loss in an autosomal recessive manner based on its predicted impact on the protein.

#	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		2	not provided	2	not provided

Last Updated: Oct 13, 2024

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