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NM_001042432.2(CLN3):c.1000C>T (p.Arg334Cys)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
4 (Most recent: Jan 7, 2021)
Last evaluated:
Jul 9, 2020
Accession:
VCV000056243.5
Variation ID:
56243
Description:
single nucleotide variant
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NM_001042432.2(CLN3):c.1000C>T (p.Arg334Cys)

Allele ID
70882
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
16p12.1
Genomic location
16: 28482161 (GRCh38) GRCh38 UCSC
16: 28493482 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000016.10:g.28482161G>A
NG_008654.2:g.15142C>T
NM_000086.2:c.1000C>T NP_000077.1:p.Arg334Cys missense
... more HGVS
Protein change
R334C, R256C, R234C, R280C, R310C
Other names
-
Canonical SPDI
NC_000016.10:28482160:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00000
Links
UniProtKB: Q13286#VAR_005135
dbSNP: rs386833694
ClinGen: CA263593
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 2 criteria provided, multiple submitters, no conflicts Jul 9, 2020 RCV000588369.4
Likely pathogenic 2 no assertion criteria provided Oct 16, 2018 RCV000049655.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
CLN3 - - GRCh38
GRCh37
617 681

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Mar 21, 2019)
criteria provided, single submitter
Method: clinical testing
Neuronal ceroid lipofuscinosis
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000697651.2
Submitted: (Sep 24, 2019)
Evidence details
Publications
PubMed (6)
Comment:
Variant summary: CLN3 c.1000C>T (p.Arg334Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging … (more)
Pathogenic
(Jul 09, 2020)
criteria provided, single submitter
Method: clinical testing
Neuronal ceroid lipofuscinosis
Allele origin: germline
Invitae
Accession: SCV001232832.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (10)
Comment:
This sequence change replaces arginine with cysteine at codon 334 of the CLN3 protein (p.Arg334Cys). The arginine residue is highly conserved and there is a … (more)
probable-pathogenic
(-)
no assertion criteria provided
Method: not provided
Juvenile neuronal ceroid lipofuscinosis
Allele origin: not provided
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)
Accession: SCV000082062.1
Submitted: (May 19, 2013)
Comment:
FinDis database variant: This variant was not found or characterized by our laboratory, data were collected from public sources: see reference
Evidence details
Comment:
Converted during submission to Likely pathogenic.
Likely pathogenic
(Oct 16, 2018)
no assertion criteria provided
Method: clinical testing
Neuronal ceroid lipofuscinosis 3
Allele origin: unknown
Counsyl
Accession: SCV001132155.1
Submitted: (Aug 05, 2019)
Evidence details
Publications
PubMed (6)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
The neuronal ceroid lipofuscinoses program: A translational research experience in Argentina. Kohan R Biochimica et biophysica acta 2015 PMID: 25976102
The role of nonsense-mediated decay in neuronal ceroid lipofuscinosis. Miller JN Human molecular genetics 2013 PMID: 23539563
Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses. Kousi M Human mutation 2012 PMID: 21990111
Juvenile neuronal ceroid lipofuscinosis: clinical course and genetic studies in Spanish patients. Pérez-Poyato MS Journal of inherited metabolic disease 2011 PMID: 21499717
Genotype does not predict severity of behavioural phenotype in juvenile neuronal ceroid lipofuscinosis (Batten disease). Adams HR Developmental medicine and child neurology 2010 PMID: 20187884
The fission yeast model for the lysosomal storage disorder Batten disease predicts disease severity caused by mutations in CLN3. Haines RL Disease models & mechanisms 2009 PMID: 19132115
Increased expression of lysosomal acid phosphatase in CLN3-defective cells and mouse brain tissue. Pohl S Journal of neurochemistry 2007 PMID: 17868323
Nitric oxide signaling is disrupted in the yeast model for Batten disease. Osório NS Molecular biology of the cell 2007 PMID: 17475770
btn1, the Schizosaccharomyces pombe homologue of the human Batten disease gene CLN3, regulates vacuole homeostasis. Gachet Y Journal of cell science 2005 PMID: 16291725
Motifs within the CLN3 protein: modulation of cell growth rates and apoptosis. Persaud-Sawin DA Human molecular genetics 2002 PMID: 12189165
CLN3 disease process: missense point mutations and protein depletion in vitro. Golabek AA European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 2001 PMID: 11589014
CLN3 protein regulates lysosomal pH and alters intracellular processing of Alzheimer's amyloid-beta protein precursor and cathepsin D in human cells. Golabek AA Molecular genetics and metabolism 2000 PMID: 10924275
Batten disease: evaluation of CLN3 mutations on protein localization and function. Haskell RE Human molecular genetics 2000 PMID: 10749980
A yeast model for the study of Batten disease. Pearce DA Proceedings of the National Academy of Sciences of the United States of America 1998 PMID: 9618513
Spectrum of mutations in the Batten disease gene, CLN3. Munroe PB American journal of human genetics 1997 PMID: 9311735

Text-mined citations for rs386833694...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 30, 2021