NM_000083.3(CLCN1):c.1437_1450del (p.Pro480fs) AND Congenital myotonia, autosomal recessive form

Germline classification:: Pathogenic/Likely pathogenic (7 submissions)
Last evaluated:: Mar 17, 2026
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002259330.11

Allele description [Variation Report for NM_000083.3(CLCN1):c.1437_1450del (p.Pro480fs)]

NM_000083.3(CLCN1):c.1437_1450del (p.Pro480fs)

Gene:

CLCN1:chloride voltage-gated channel 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

7q34

Genomic location:

Preferred name:

NM_000083.3(CLCN1):c.1437_1450del (p.Pro480fs)

Other names:

dbSNP ID: rs768119034

HGVS:

NC_000007.14:g.143339288_143339301del
NG_009815.2:g.28163_28176del
NM_000083.3:c.1437_1450delMANE SELECT
NP_000074.3:p.Pro480fs
NC_000007.13:g.143036380_143036393del
NC_000007.13:g.143036381_143036394del
NG_009815.1:g.28163_28176del
NM_000083.2:c.1437_1450delACCCTGCGGAGGCT
NM_000083.3:c.1437_1450del14MANE SELECT
NM_000083.3:c.1437_1450delACCCTGCGGAGGCTMANE SELECT
NR_046453.2:n.1392_1405del
p.Pro480Hisfs*24

Protein change:

P480fs

Links:

OMIM: 118425.0009; dbSNP: rs768119034

Molecular consequence:

NM_000083.3:c.1437_1450del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_046453.2:n.1392_1405del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Congenital myotonia, autosomal recessive form
Synonyms:: BECKER DISEASE; Becker Generalized Myotonia
Identifiers:: MONDO: MONDO:0009715; MedGen: C0751360; Orphanet: 614; OMIM: 255700

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
SCV000039380	OMIM	no assertion criteria provided	Pathogenic (May 1, 2009)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 7951215, 7581380, 18337100 Becker, P. E. Myotonia Congenita and Syndromes associated with Myotonia: Clinical-Genetic Studies of the Nondystrophic Myotonias. Stuttgart: Georg Thieme (pub.) 1977.,
SCV004100818	Clinical Omics and Informatics (COIN) Unit, Neuroscience Institute, University Of Cape Town - International Center for Genomic Medicine for Neuromuscular Disease (ICGNMD)	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 22, 2024)	germline	research	PubMed (2) [See all records that cite these PMIDs] 37712079, 25741868
SCV004171141	Institute of Human Genetics, University Hospital of Duesseldorf	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	not provided	PubMed (1) [See all records that cite this PMID]
SCV005038722	Department Of Human Genetics, Institute Of Clinical And Translational Research, Biomedical Research Center, Slovak Academy Of Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	germline	research	PubMed (2) [See all records that cite these PMIDs] 24349310, 25741868
SCV007580587	First Genomix Gene Laboratory, Genetic Diagnostics Department	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 10, 2025)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV007584820	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Mar 17, 2026)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24349310, 23893571 Citation Link,
SCV007607625	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 26, 2025)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 7951215, 25741868

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	4	3	not provided	not provided	not provided	research, not provided, clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Myotonia levior is a chloride channel disorder.

Lehmann-Horn F, Mailänder V, Heine R, George AL.

Hum Mol Genet. 1995 Aug;4(8):1397-402.

PubMed [citation]

PMID:: 7581380

Clinical, electrophysiologic, and genetic study of non-dystrophic myotonia in French-Canadians.

Dupré N, Chrestian N, Bouchard JP, Rossignol E, Brunet D, Sternberg D, Brais B, Mathieu J, Puymirat J.

Neuromuscul Disord. 2009 May;19(5):330-4. doi: 10.1016/j.nmd.2008.01.007. Epub 2008 Mar 11.

PubMed [citation]

PMID:: 18337100

See all PubMed Citations (7)

Details of each submission

From OMIM, SCV000039380.1

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

Description

In patients with Becker myotonia (255700), Meyer-Kleine et al. (1994) identified a 14-bp deletion in exon 13 of the CLCN1 gene.

In a family in which the index patient and his mother had been examined by Becker (1977), who classified their disorder as dominant myotonia congenita, Lehmann-Horn et al. (1995) found that the proband was homozygous for a 14-bp deletion (involving nucleotides 1437-1450) in exon 13 of the CLCN1 gene. Both nonmyotonic sons of the index patient were heterozygous for the deletion.

In French Canadian patients with recessive myotonia, Dupre et al. (2009) found that homozygosity for the 14-bp deletion resulted in a severe phenotype with generalized hypertrophy, moderate myotonia, and transient weakness.

#	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		not provided	not provided	not provided	not provided

From Clinical Omics and Informatics (COIN) Unit, Neuroscience Institute, University Of Cape Town - International Center for Genomic Medicine for Neuromuscular Disease (ICGNMD), SCV004100818.4

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

Description

Proband also has heterozygous pathogenic CLCN1 p.Arg894Ter variant (not confirmed in trans).

Description

PM2_supporting: this variant is absent from gnomAD v4.0 (adequate coverage >20X confirmed). The highest population allele frequency in gnomAD v3.1.2 is 0.00016 (0.016%; 11/68038 alleles in European non-Finnish population). PM3_verystrong: this variant has been found in a compound heterozygous state in multiple individuals with AR myotonia congenital (>4 points). PVS1 met: frameshift variant predicted to undergo NMD. Exon is present in a biologically relevant transcript in a gene where LOF is a known mechanism of disease. PS4 met: this variant has been described in more than 10 unrelated probands with consistent phenotype for disorder. Sequencing funded by the International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD): https://www.ucl.ac.uk/genomic-medicine-neuromuscular-diseases/.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	1	not provided

From Institute of Human Genetics, University Hospital of Duesseldorf, SCV004171141.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Department Of Human Genetics, Institute Of Clinical And Translational Research, Biomedical Research Center, Slovak Academy Of Sciences, SCV005038722.1

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

Description

The c.1437_1450del (p.(Pro480Hisfs*24)) variant was found in a heterozygous state in 3 Slovak patients with Myotonia congenita and in all of them also the second Likely Pathogenic variant was found: in two of them it was c.2680C>T (p.(Arg894*), whereas in the last one c.2364+2T>C splicing variant. The c.1437_1450del variant is listed as a disease-causing in the HGMD database (CD941645). GnomAD Exomes Version: 4.0 indicates the frequency of f = 0.000121.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		3	not provided	3	not provided

From First Genomix Gene Laboratory, Genetic Diagnostics Department, SCV007580587.1

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

Description

As part of Carrier Screening testing performed at First Genomix, this variant was identified in a heterozygous state in a patient who is not affected with this condition.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		1	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV007584820.1

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

Description

Variant summary: CLCN1 c.1437_1450del14 (p.Pro480HisfsX24) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 5.6e-05 in 251488 control chromosomes. This frequency is not significantly higher than estimated for disease-causing variants in CLCN1, allowing no conclusion about variant significance. c.1437_1450del14 has been observed in multiple individuals affected with autosomal recessive myotonia congenita (e.g. Skalova_2013) and in individuals affected with autosomal dominant myotonia congenita (e.g. Richardson_2014). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 24349310, 23893571). ClinVar contains an entry for this variant (Variation ID: 279778). Based on the evidence outlined above, the variant was classified as pathogenic for autosomal recessive and autosomal dominant myotonia congenita.

#	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

From 3billion, SCV007607625.1

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

Description

The variant is observed at an extremely low frequency in the gnomAD v4.1.0 dataset (total allele frequency: 0.012%). Predicted Consequence/Location: Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000279778 /PMID: 7951215 /3billion dataset). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 20, 2026

Relating variation to medicine