NM_000083.3(CLCN1):c.1261dup (p.Arg421fs) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: May 5, 2023
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:: RCV000516577.11

Allele description [Variation Report for NM_000083.3(CLCN1):c.1261dup (p.Arg421fs)]

NM_000083.3(CLCN1):c.1261dup (p.Arg421fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

7q34

Genomic location:

Preferred name:

NM_000083.3(CLCN1):c.1261dup (p.Arg421fs)

HGVS:

NC_000007.14:g.143332733dup
NG_009815.1:g.21608dup
NM_000083.3:c.1261dupMANE SELECT
NP_000074.3:p.Arg421fs
NC_000007.13:g.143029822_143029823insC
NC_000007.13:g.143029826dup
NM_000083.2:c.1261dup
NM_000083.2:c.1261dupC
p.Arg421Profs*9

Protein change:

R421fs

Links:

dbSNP: rs763633152

NCBI 1000 Genomes Browser:

rs763633152

Molecular consequence:

NM_000083.3:c.1261dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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uncharacterized protein Dmel_CG9106, isoform B [Drosophila melanogaster]
uncharacterized protein Dmel_CG9106, isoform B [Drosophila melanogaster]
gi|24642128|ref|NP_727838.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000612757	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (May 5, 2023)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 29606556, 8533761, 26467025
SCV002017370	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 5, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002097433	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Aug 11, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000612757

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Pathogenic
(May 5, 2023)

unknown

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002017370

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 5, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002097433

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Aug 11, 2022)

germline

clinical testing

Citation Link

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	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Prevalence and mutation spectrum of skeletal muscle channelopathies in the Netherlands.

Stunnenberg BC, Raaphorst J, Deenen JCW, Links TP, Wilde AA, Verbove DJ, Kamsteeg EJ, van den Wijngaard A, Faber CG, van der Wilt GJ, van Engelen BGM, Drost G, Ginjaar HB.

Neuromuscul Disord. 2018 May;28(5):402-407. doi: 10.1016/j.nmd.2018.03.006. Epub 2018 Mar 9.

PubMed [citation]

PMID:: 29606556

Spectrum of mutations in the major human skeletal muscle chloride channel gene (CLCN1) leading to myotonia.

Meyer-Kleine C, Steinmeyer K, Ricker K, Jentsch TJ, Koch MC.

Am J Hum Genet. 1995 Dec;57(6):1325-34.

PubMed [citation]

PMID:: 8533761
PMCID:: PMC1801423

See all PubMed Citations (4)

Details of each submission

From Athena Diagnostics, SCV000612757.3

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

Description

This variant is expected to result in the loss of a functional protein. The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been reported in multiple families with autosomal recessive myotonia congenita (PMID: 29606556, 8533761).

#	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 Revvity Omics, Revvity, SCV002017370.3

#	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 GeneDx, SCV002097433.3

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

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 8533761, 31589614, 35170402, 35350395)

#	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: Sep 29, 2024

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