NM_000083.3(CLCN1):c.979G>A (p.Val327Ile) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Jun 27, 2025
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:: RCV000517879.10

Allele description [Variation Report for NM_000083.3(CLCN1):c.979G>A (p.Val327Ile)]

NM_000083.3(CLCN1):c.979G>A (p.Val327Ile)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

7q34

Genomic location:

Preferred name:

NM_000083.3(CLCN1):c.979G>A (p.Val327Ile)

HGVS:

NC_000007.14:g.143330897G>A
NG_009815.2:g.19772G>A
NM_000083.3:c.979G>AMANE SELECT
NP_000074.3:p.Val327Ile
NC_000007.13:g.143027990G>A
NG_009815.1:g.19772G>A
NM_000083.2:c.979G>A
NR_046453.2:n.1084G>A

Protein change:

V327I

Links:

dbSNP: rs774396430

NCBI 1000 Genomes Browser:

rs774396430

Molecular consequence:

NM_000083.3:c.979G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_046453.2:n.1084G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

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
SCV000612810	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Dec 20, 2015)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 23516313, 11933197, 23810313, 11840191, 17932099, 7951242, 26467025
SCV001778998	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Jun 27, 2025)	germline	clinical testing	Citation Link,
SCV002022570	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 1, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005413813	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 4, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 17932099, 23516313, 32670189, 33263785, 34529042, 36796140, 7951242, 25741868

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Myotonia caused by mutations in the muscle chloride channel gene CLCN1.

Pusch M.

Hum Mutat. 2002 Apr;19(4):423-34. Review.

PubMed [citation]

PMID:: 11933197

Muscle MRI reveals distinct abnormalities in genetically proven non-dystrophic myotonias.

Morrow JM, Matthews E, Raja Rayan DL, Fischmann A, Sinclair CD, Reilly MM, Thornton JS, Hanna MG, Yousry TA.

Neuromuscul Disord. 2013 Aug;23(8):637-46. doi: 10.1016/j.nmd.2013.05.001. Epub 2013 Jun 27.

PubMed [citation]

PMID:: 23810313
PMCID:: PMC3744809

See all PubMed Citations (12)

Details of each submission

From Athena Diagnostics, SCV000612810.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

#	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 GeneDx, SCV001778998.2

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

Description

Expression of V327I cRNA into Xenopus oocytes yielded CLC-1 currents that were indistinguishable from wild type, which supports the hypothesis that the c.979 G>A variant exerts its effect by affecting splicing (PMID: 7951242); Not observed at significant frequency in large population cohorts (gnomAD); Alters the last nucleotide of the exon and is predicted to damage the splice donor site but the effect on protein function is unclear; This variant is associated with the following publications: (PMID: 17932099, 11933197, 23516313, 22187529, 21387378, 24037712, 15786415, 8533761, 32010054, 11840191, 23810313, 32670189, 33263785, 34529042, 7951242, 32117024, 36796140)

#	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 Revvity Omics, Revvity, SCV002022570.3

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

#	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 Mayo Clinic Laboratories, Mayo Clinic, SCV005413813.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (8)

Description

PP1, PP3, PP4, PM2_moderate, PM3, PS4

#	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		1	not provided	not provided	not provided

Last Updated: Jul 5, 2025

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