NM_174878.3(CLRN1):c.419T>A (p.Leu140Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 8, 2019
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:: RCV001050877.8

Allele description [Variation Report for NM_174878.3(CLRN1):c.419T>A (p.Leu140Ter)]

NM_174878.3(CLRN1):c.419T>A (p.Leu140Ter)

Gene:

CLRN1:clarin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q25.1

Genomic location:

Preferred name:

NM_174878.3(CLRN1):c.419T>A (p.Leu140Ter)

HGVS:

NC_000003.12:g.150941596A>T
NG_009168.1:g.36404T>A
NM_001195794.1:c.419T>A
NM_001256819.2:c.*33T>A
NM_052995.2:c.191T>A
NM_174878.3:c.419T>AMANE SELECT
NP_001182723.1:p.Leu140Ter
NP_443721.1:p.Leu64Ter
NP_777367.1:p.Leu140Ter
LRG_700t1:c.419T>A
LRG_700t2:c.191T>A
LRG_700:g.36404T>A
LRG_700p1:p.Leu140Ter
LRG_700p2:p.Leu64Ter
NC_000003.11:g.150659383A>T
NM_174878.2:c.419T>A
NR_046380.3:n.589T>A

Protein change:

L140*

Links:

dbSNP: rs1713844309

NCBI 1000 Genomes Browser:

rs1713844309

Molecular consequence:

NM_001256819.2:c.*33T>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NR_046380.3:n.589T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001195794.1:c.419T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_052995.2:c.191T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_174878.3:c.419T>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001215006	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 8, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 2145752, 22681893, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001215006

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 8, 2019)

germline

clinical testing

PubMed (3)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Use of technetium-99m sestamibi to determine the size of the myocardial area perfused by a coronary artery.

Braat SH, de Swart H, Janssen JH, Brugada P, Rigo P, Wellens HJ.

Am J Cardiol. 1990 Oct 16;66(13):85E-90E.

PubMed [citation]

PMID:: 2145752

Extended mutation spectrum of Usher syndrome in Finland.

Västinsalo H, Jalkanen R, Bergmann C, Neuhaus C, Kleemola L, Jauhola L, Bolz HJ, Sankila EM.

Acta Ophthalmol. 2013 Jun;91(4):325-34. doi: 10.1111/j.1755-3768.2012.02397.x. Epub 2012 Jun 8.

PubMed [citation]

PMID:: 22681893

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001215006.5

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the CLRN1 protein. A different variant that disrupt this region (p.Tyr176*) has been determined to be pathogenic (PMID: 2145752, 22681893). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with CLRN1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the CLRN1 gene (p.Leu140*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 93 amino acids of the CLRN1 protein.

#	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

Last Updated: Sep 29, 2024

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