NM_000083.3(CLCN1):c.501C>G (p.Phe167Leu) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Conflicting interpretations of pathogenicity (5 submissions)
Last evaluated:: Mar 29, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000711233.28

Allele description

NM_000083.3(CLCN1):c.501C>G (p.Phe167Leu)

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.501C>G (p.Phe167Leu)

HGVS:

NC_000007.14:g.143321432C>G
NG_009815.2:g.10307C>G
NM_000083.3:c.501C>GMANE SELECT
NP_000074.3:p.Phe167Leu
NC_000007.13:g.143018525C>G
NG_009815.1:g.10307C>G
NM_000083.2:c.501C>G
NR_046453.2:n.603C>G
P35523:p.Phe167Leu

Protein change:

F167L

Links:

UniProtKB: P35523#VAR_001588; dbSNP: rs149729531

NCBI 1000 Genomes Browser:

rs149729531

Molecular consequence:

NM_000083.3:c.501C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_046453.2:n.603C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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
SCV000841565	Athena Diagnostics Inc	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Aug 4, 2021)	unknown	clinical testing	PubMed (26) [See all records that cite these PMIDs] 34106991, 32670189, 32117024, 16770776, 24304580, 24349310, 23933576, 26510092, 23739125, 24452722, 22109722, 24037712, 27614575, 28993909, 27266866, 10690989, 17654559, 17932099, 18337730, 21221019, 21698652, 22094069, 22407275, 7874130, 8533761, 26467025
SCV000892807	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Mar 1, 2022)	germline	clinical testing	Citation Link,
SCV002583811	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 7, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003830777	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 21, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004224117	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 29, 2023)	germline	clinical testing	PubMed (17) [See all records that cite these PMIDs] 10690989, 21221019, 22407275, 22521272, 23933576, 24304580, 26510092, 27266866, 27614575, 27884173, 32117024, 32670189, 33263785, 34106991, 34426522, 34529042, 25741868

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	7	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Acetazolamide acts directly on the human skeletal muscle chloride channel.

Eguchi H, Tsujino A, Kaibara M, Hayashi H, Shirabe S, Taniyama K, Eguchi K.

Muscle Nerve. 2006 Sep;34(3):292-7.

PubMed [citation]

PMID:: 16770776

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, Zídková J, Voháňka S, Mazanec R, Mušová Z, Vondráček P, Mrázová L, Kraus J, Réblová K, Fajkusová L.

PLoS One. 2013;8(12):e82549. doi: 10.1371/journal.pone.0082549.

PubMed [citation]

PMID:: 24349310
PMCID:: PMC3859631

See all PubMed Citations (32)

Details of each submission

From Athena Diagnostics Inc, SCV000841565.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (26)

Description

This variant is statistically more frequent in affected individuals than in the general population and/or healthy controls. Therefore, the frequency of this variant in the general population is consistent with pathogenicity (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)). This variant has been reported in multiple families with autosomal recessive myotonia congenita (PMID: 18337730, 21221019, 24037712, 23739125). Although there are heterozygous carriers with disease, this variant has also been reported in asymptomatic individuals (PMID: 17932099, 21698652, 26510092, 7874130, 27614575). Therefore, the data only supports a recessive association with CLCN1-related conditions. In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic.

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

From CeGaT Center for Human Genetics Tuebingen, SCV000892807.22

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

Description

CLCN1: PM3, PM2:Supporting

#	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		7	not provided	not provided	not provided

From Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center, SCV002583811.1

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

Description

BP4

#	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, SCV003830777.2

#	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, SCV004224117.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (17)

#	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: Apr 20, 2024

ClinVar

Relating variation to medicine