NM_000083.3(CLCN1):c.1650G>A (p.Thr550=) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 5, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001047235.10

Allele description [Variation Report for NM_000083.3(CLCN1):c.1650G>A (p.Thr550=)]

NM_000083.3(CLCN1):c.1650G>A (p.Thr550=)

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.1650G>A (p.Thr550=)

HGVS:

NC_000007.14:g.143341996G>A
NG_009815.2:g.30871G>A
NM_000083.3:c.1650G>AMANE SELECT
NP_000074.3:p.Thr550=
NC_000007.13:g.143039089G>A
NG_009815.1:g.30871G>A
NM_000083.2:c.1650G>A
NR_046453.2:n.1605G>A

Links:

dbSNP: rs778647317

NCBI 1000 Genomes Browser:

rs778647317

Molecular consequence:

NR_046453.2:n.1605G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000083.3:c.1650G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:: Congenital myotonia, autosomal recessive form
Synonyms:: Myotonia congenita autosomal recessive; Becker disease; Myotonia generalized; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009715; MedGen: C0751360; Orphanet: 614; OMIM: 255700

Name:: Congenital myotonia, autosomal dominant form (THD)
Synonyms:: Myotonia congenita autosomal dominant; Thomsen disease; Thomsen's disease
Identifiers:: MONDO: MONDO:0008055; MedGen: C2936781; Orphanet: 614; OMIM: 160800

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001211175	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 5, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23516313, 31772215, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001211175

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 5, 2024)

germline

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Prevalence study of genetically defined skeletal muscle channelopathies in England.

Horga A, Raja Rayan DL, Matthews E, Sud R, Fialho D, Durran SC, Burge JA, Portaro S, Davis MB, Haworth A, Hanna MG.

Neurology. 2013 Apr 16;80(16):1472-5. doi: 10.1212/WNL.0b013e31828cf8d0. Epub 2013 Mar 20.

PubMed [citation]

PMID:: 23516313
PMCID:: PMC3662361

Myotonia in a patient with a mutation in an S4 arginine residue associated with hypokalaemic periodic paralysis and a concomitant synonymous CLCN1 mutation.

Thor MG, Vivekanandam V, Sampedro-Castañeda M, Tan SV, Suetterlin K, Sud R, Durran S, Schorge S, Kullmann DM, Hanna MG, Matthews E, Männikkö R.

Sci Rep. 2019 Nov 26;9(1):17560. doi: 10.1038/s41598-019-54041-0.

PubMed [citation]

PMID:: 31772215
PMCID:: PMC6879752

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001211175.5

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

Description

This sequence change affects codon 550 of the CLCN1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the CLCN1 protein. This variant is present in population databases (rs778647317, gnomAD 0.003%). This variant has been observed in individual(s) with autosomal recessive myotonia congenita (PMID: 23516313, 31772215). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 844401). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.

#	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

Last Updated: Sep 29, 2024

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