NM_052995.2(CLRN1):c.300T>G (p.Tyr100Ter) AND Rare genetic deafness

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 26, 2013
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:: RCV000844623.5

Allele description [Variation Report for NM_052995.2(CLRN1):c.300T>G (p.Tyr100Ter)]

NM_052995.2(CLRN1):c.300T>G (p.Tyr100Ter)

Gene:

CLRN1:clarin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q25.1

Genomic location:

Preferred name:

NM_052995.2(CLRN1):c.300T>G (p.Tyr100Ter)

HGVS:

NC_000003.12:g.150928107A>C
NG_009168.1:g.49893T>G
NM_001195794.1:c.567T>G
NM_001256819.2:c.*142T>G
NM_052995.2:c.300T>G
NM_174878.3:c.528T>GMANE SELECT
NP_001182723.1:p.Tyr189Ter
NP_443721.1:p.Tyr100Ter
NP_777367.1:p.Tyr176Ter
LRG_700t1:c.567T>G
LRG_700t2:c.300T>G
LRG_700:g.49893T>G
LRG_700p1:p.Tyr189Ter
LRG_700p2:p.Tyr100Ter
NC_000003.11:g.150645894A>C
NM_174878.3:c.528T>G
NR_046380.3:n.737T>G
c.567T>G (p.Tyr189*)
p.Tyr176X

Protein change:

Y100*; TYR176TER

Links:

OMIM: 606397.0001; dbSNP: rs121908140

NCBI 1000 Genomes Browser:

rs121908140

Molecular consequence:

NM_001195794.1:c.567T>G - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

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

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
SCV000203992	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Nov 26, 2013)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 11524702, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000203992

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Nov 26, 2013)

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	3	2	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in a novel gene with transmembrane domains underlie Usher syndrome type 3.

Joensuu T, Hämäläinen R, Yuan B, Johnson C, Tegelberg S, Gasparini P, Zelante L, Pirvola U, Pakarinen L, Lehesjoki AE, de la Chapelle A, Sankila EM.

Am J Hum Genet. 2001 Oct;69(4):673-84. Epub 2001 Aug 27. Erratum in: Am J Hum Genet 2001 Nov;69(5):1160.

PubMed [citation]

PMID:: 11524702
PMCID:: PMC1226054

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, SCV000203992.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	PubMed (2)

Description

The Tyr176X variant in CLRN1 has been previously identified in 52 homozygous and 2 compound heterozygous individuals with Usher syndrome type III (Joensuu 2001) . This variant has been identified in 1/8,600 European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs1 21908140). Although this variant has been seen in the general population, its fr equency is low enough to be consistent with a recessive carrier frequency. This nonsense variant leads to a premature termination codon at position 176, which i s predicted to lead to a truncated or absent protein. In summary, this variant m eets our criteria to be classified as pathogenic in a recessive manner for Ushe r syndrome (http://pcpgm.partners.org/LMM).

#	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		3	not provided	2	not provided

Last Updated: Feb 20, 2024

ClinVar

Relating variation to medicine