NM_000083.3(CLCN1):c.1606G>A (p.Val536Ile) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Dec 19, 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:: RCV000517072.5

Allele description [Variation Report for NM_000083.3(CLCN1):c.1606G>A (p.Val536Ile)]

NM_000083.3(CLCN1):c.1606G>A (p.Val536Ile)

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.1606G>A (p.Val536Ile)

HGVS:

NC_000007.14:g.143341952G>A
NG_009815.2:g.30827G>A
NM_000083.3:c.1606G>AMANE SELECT
NP_000074.3:p.Val536Ile
NC_000007.13:g.143039045G>A
NG_009815.1:g.30827G>A
NM_000083.2:c.1606G>A
NR_046453.2:n.1561G>A

Protein change:

V536I

Links:

dbSNP: rs777685454

NCBI 1000 Genomes Browser:

rs777685454

Molecular consequence:

NM_000083.3:c.1606G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_046453.2:n.1561G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV000612766	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Likely pathogenic (Dec 7, 2016)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23152584, 26467025
SCV003837035	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Dec 19, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000612766

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Likely pathogenic
(Dec 7, 2016)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV003837035

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Dec 19, 2023)

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	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

New immunohistochemical method for improved myotonia and chloride channel mutation diagnostics.

Raheem O, Penttilä S, Suominen T, Kaakinen M, Burge J, Haworth A, Sud R, Schorge S, Haapasalo H, Sandell S, Metsikkö K, Hanna M, Udd B.

Neurology. 2012 Nov 27;79(22):2194-200. doi: 10.1212/WNL.0b013e31827595e2. Epub 2012 Nov 14.

PubMed [citation]

PMID:: 23152584
PMCID:: PMC3570820

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From Athena Diagnostics, SCV000612766.1

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

#	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, SCV003837035.2

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

Description

Reported in a heterozygous state in an individual with a personal and family history of myotonia congenita (PMID: 28325641); Reported in patients with myotonia who also harbored as second CLCN1 variant, phase unknown (PMID: 23152584, 34529042); In silico analysis supports that this missense variant does not alter protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23152584, 31589614, 29405036, 34529042, 24304580, 28325641)

#	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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