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NM_000083.3(CLCN1):c.568_569delinsTC (p.Gly190Ser)

Conflicting interpretations of pathogenicity​

Likely pathogenic(1);Pathogenic(4);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
6 (Most recent: Sep 13, 2021)
Last evaluated:
Apr 23, 2021
Variation ID:
2bp indel

NM_000083.3(CLCN1):c.568_569delinsTC (p.Gly190Ser)

Allele ID
Variant type
Variant length
2 bp
Cytogenetic location
Genomic location
7: 143321720-143321721 (GRCh38) GRCh38 UCSC
7: 143018813-143018814 (GRCh37) GRCh37 UCSC
Nucleotide Protein Molecular
... more HGVS
Protein change
Other names
Canonical SPDI
Functional consequence
Global minor allele frequency (GMAF)

Allele frequency
ClinGen: CA276131
dbSNP: rs797045032

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 1 criteria provided, single submitter Nov 26, 2013 RCV000191069.1
Pathogenic 1 criteria provided, single submitter Oct 15, 2020 RCV000530150.6
Pathogenic 1 criteria provided, single submitter Jan 1, 2017 RCV000626583.1
Conflicting interpretations of pathogenicity 3 criteria provided, conflicting interpretations Apr 23, 2021 RCV000489144.4
Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
CLCN1 - - GRCh38
621 666

Submitted interpretations and evidence

(Last evaluated)
Review status
(Assertion criteria)
Submitter Supporting information
Likely pathogenic
(Nov 26, 2013)
criteria provided, single submitter
Method: clinical testing
Congenital myotonia, autosomal recessive form
(Autosomal recessive inheritance)
Allele origin: germline
Baylor Genetics
Study: Adult_WES
Accession: SCV000245461.1
Submitted: (Aug 17, 2015)
Evidence details
PubMed (1)
Likely pathogenicity based on finding it once in our laboratory with a known pathogenic missense variant (F167L; phase unknown) in a 46-year-old male with heart … (more)
Uncertain significance
(Jan 13, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000704674.2
Submitted: (Sep 19, 2018)
Evidence details
Other databases…
(Oct 15, 2020)
criteria provided, single submitter
Method: clinical testing
Congenital myotonia, autosomal recessive form
Congenital myotonia, autosomal dominant form
Allele origin: germline
Accession: SCV000649786.6
Submitted: (Jan 07, 2021)
Evidence details
PubMed (9)
This sequence change replaces glycine with serine at codon 190 of the CLCN1 protein (p.Gly190Ser). The glycine residue is highly conserved and there is a … (more)
(Apr 23, 2021)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: unknown
Athena Diagnostics Inc
Accession: SCV000612791.3
Submitted: (Sep 13, 2021)
Evidence details
PubMed (14)
This variant is statistically more frequent in affected individuals than in the general population and/or healthy controls and therefore is consistent with pathogenicity ( At … (more)
(Jan 01, 2017)
criteria provided, single submitter
Method: clinical testing
EMG: myotonic discharges
Myocardial infarction
Myotonia of the upper limb
Allele origin: unknown
Centre for Mendelian Genomics,University Medical Centre Ljubljana
Accession: SCV000747284.1
Submitted: (Dec 08, 2017)
Evidence details
(Mar 13, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
Accession: SCV000577243.4
Submitted: (Jan 29, 2019)
Evidence details
The c.568_569delGGinsTC variant in the CLCN1 gene has been previously reported in thehomozygous, compound heterozygous, and heterozygous states in association with myotoniacongenita (Shalata et al., … (more)

Functional evidence

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

Title Author Journal Year Link
Pathomechanisms of a <i>CLCN1</i> Mutation Found in a Russian Family Suffering From Becker's Myotonia. Altamura C Frontiers in neurology 2020 PMID: 33013670
Congenital myotonia: a review of twenty cases and a new splice-site mutation in the CLCN1 gene. Özgün N The Turkish journal of pediatrics 2020 PMID: 32558419
<i>CLCN1</i> Molecular Characterization in 19 South-Italian Patients With Dominant and Recessive Type of Myotonia Congenita. Orsini C Frontiers in neurology 2020 PMID: 32117024
Prevalence and mutation spectrum of skeletal muscle channelopathies in the Netherlands. Stunnenberg BC Neuromuscular disorders : NMD 2018 PMID: 29606556
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Targeted Next Generation Sequencing in patients with Myotonia Congenita. Ferradini V Clinica chimica acta; international journal of clinical chemistry 2017 PMID: 28427807
Molecular diagnostic experience of whole-exome sequencing in adult patients. Posey JE Genetics in medicine : official journal of the American College of Medical Genetics 2016 PMID: 26633545
Clinical, Molecular, and Functional Characterization of CLCN1 Mutations in Three Families with Recessive Myotonia Congenita. Portaro S Neuromolecular medicine 2015 PMID: 26007199
CLCN1 mutations in Czech patients with myotonia congenita, in silico analysis of novel and known mutations in the human dimeric skeletal muscle chloride channel. Skálová D PloS one 2013 PMID: 24349310
Functional characterization of ClC-1 mutations from patients affected by recessive myotonia congenita presenting with different clinical phenotypes. Desaphy JF Experimental neurology 2013 PMID: 23933576
A large cohort of myotonia congenita probands: novel mutations and a high-frequency mutation region in exons 4 and 5 of the CLCN1 gene. Brugnoni R Journal of human genetics 2013 PMID: 23739125
Stiffness as a presenting symptom of an odd clinical condition caused by multiple sclerosis and myotonia congenita. Portaro S Neuromuscular disorders : NMD 2013 PMID: 22921319
[The spectrum of CLCN1 gene mutations in patients with nondystrophic Thomsen's and Becker's myotonias]. Ivanova EA Genetika 2012 PMID: 23113340
Myotonia congenita: novel mutations in CLCN1 gene and functional characterizations in Italian patients. Ulzi G Journal of the neurological sciences 2012 PMID: 22521272
Low-rate repetitive nerve stimulation protocol in an Italian cohort of patients affected by recessive myotonia congenita. Modoni A Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society 2011 PMID: 21221019
Myotonia congenita in a large consanguineous Arab family: insight into the clinical spectrum of carriers and double heterozygotes of a novel mutation in the chloride channel CLCN1 gene. Shalata A Muscle & nerve 2010 PMID: 19697366 - - - -

Text-mined citations for rs797045032...

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 Sep 18, 2021