NM_000083.3(CLCN1):c.1453A>G (p.Met485Val) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: Jan 13, 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:: RCV000342021.30

Allele description [Variation Report for NM_000083.3(CLCN1):c.1453A>G (p.Met485Val)]

NM_000083.3(CLCN1):c.1453A>G (p.Met485Val)

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.1453A>G (p.Met485Val)

HGVS:

NC_000007.14:g.143339304A>G
NG_009815.2:g.28179A>G
NM_000083.3:c.1453A>GMANE SELECT
NP_000074.3:p.Met485Val
NC_000007.13:g.143036397A>G
NG_009815.1:g.28179A>G
NM_000083.2:c.1453A>G
NR_046453.2:n.1408A>G
P35523:p.Met485Val

Protein change:

M485V

Links:

UniProtKB: P35523#VAR_001609; dbSNP: rs146457619

NCBI 1000 Genomes Browser:

rs146457619

Molecular consequence:

NM_000083.3:c.1453A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_046453.2:n.1408A>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

PREDICTED: Homo sapiens RAB, member of RAS oncogene family like 2A (RABL2A), tra...
PREDICTED: Homo sapiens RAB, member of RAS oncogene family like 2A (RABL2A), transcript variant X1, mRNA
gi|2462569540|ref|XM_054340260.1|

Nucleotide
rab-like protein 2A isoform X1 [Homo sapiens]
rab-like protein 2A isoform X1 [Homo sapiens]
gi|1034611181|ref|XP_016858696.1|

Protein
rab-like protein 2A isoform X5 [Homo sapiens]
rab-like protein 2A isoform X5 [Homo sapiens]
gi|2217325162|ref|XP_047299003.1|

Protein
Homo sapiens RAB, member of RAS oncogene family like 2A (RABL2A), transcript var...
Homo sapiens RAB, member of RAS oncogene family like 2A (RABL2A), transcript variant 17, mRNA
gi|1677501501|ref|NM_001354417.2|

Nucleotide
Homo sapiens RAB, member of RAS oncogene family like 2A (RABL2A), transcript var...
Homo sapiens RAB, member of RAS oncogene family like 2A (RABL2A), transcript variant 5, mRNA
gi|1677538340|ref|NM_001306160.3|

Nucleotide

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
SCV000329931	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Sep 24, 2021)	germline	clinical testing	Citation Link,
SCV000612763	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Feb 16, 2021)	unknown	clinical testing	PubMed (15) [See all records that cite these PMIDs] 18337100, 22094069, 24037712, 23739125, 31544778, 28427807, 29606556, 25088311, 24920213, 24349310, 17932099, 8533761, 9158157, 9736777, 26467025
SCV002019324	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 13, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002563983	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Feb 1, 2019)	germline	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	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

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

Screening for mutations in Spanish families with myotonia. Functional analysis of novel mutations in CLCN1 gene.

Mazón MJ, Barros F, De la Peña P, Quesada JF, Escudero A, Cobo AM, Pascual-Pascual SI, Gutiérrez-Rivas E, Guillén E, Arpa J, Eraso P, Portillo F, Molano J.

Neuromuscul Disord. 2012 Mar;22(3):231-43. doi: 10.1016/j.nmd.2011.10.013. Epub 2011 Nov 16.

PubMed [citation]

PMID:: 22094069

See all PubMed Citations (16)

Details of each submission

From GeneDx, SCV000329931.9

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

Description

Published functional studies demonstrate variant leads to drastic reduction of single channel conductance, is strongly inwardly rectifying, and incompletely deactivates at negative voltages (Wollnik et al., 1997); This variant is associated with the following publications: (PMID: 23739125, 9736777, 32509969, 33464536, 33314145, 8533761, 25088311, 24920213, 22094069, 9158157, 28427807, 29606556, 17932099, 31544778, 32010054, 31589614)

#	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 Athena Diagnostics, SCV000612763.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (15)

Description

The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in multiple individuals with recessive myotonia congenita (PMID: 8533761, 18337100, 22094069, 24349310, 24920213). This variant is statistically more frequent in affected individuals than in the general population and/or healthy controls. Assessment of experimental evidence suggests this variant results in abnormal protein function. This variant leads to a reduction in channel conductance (PMID: 9158157). The variant is located in a region that is considered important for protein function and/or structure.

#	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, SCV002019324.3

#	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 CeGaT Center for Human Genetics Tuebingen, SCV002563983.15

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

#	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		2	not provided	not provided	not provided

Last Updated: Oct 8, 2024

ClinVar

Relating variation to medicine