NM_000083.3(CLCN1):c.742A>T (p.Lys248Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 14, 2023
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:: RCV001223937.8

Allele description [Variation Report for NM_000083.3(CLCN1):c.742A>T (p.Lys248Ter)]

NM_000083.3(CLCN1):c.742A>T (p.Lys248Ter)

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.742A>T (p.Lys248Ter)

HGVS:

NC_000007.14:g.143323354A>T
NG_009815.2:g.12229A>T
NM_000083.3:c.742A>TMANE SELECT
NP_000074.3:p.Lys248Ter
NC_000007.13:g.143020447A>T
NG_009815.1:g.12229A>T
NM_000083.2:c.742A>T
NR_046453.2:n.844A>T

Protein change:

K248*

Links:

dbSNP: rs561470261

NCBI 1000 Genomes Browser:

rs561470261

Molecular consequence:

NR_046453.2:n.844A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000083.3:c.742A>T - nonsense - [Sequence Ontology: SO:0001587]

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

Recent activity

Clear Turn Off Turn On

Danio rerio nodal-related 1 (ndr1), mRNA
Danio rerio nodal-related 1 (ndr1), mRNA
gi|1896814195|ref|NM_130966.2|

Nucleotide
PREDICTED: Danio rerio heterogeneous nuclear ribonucleoprotein C (hnrnpc), trans...
PREDICTED: Danio rerio heterogeneous nuclear ribonucleoprotein C (hnrnpc), transcript variant X2, mRNA
gi|2800564678|ref|XM_068223589.1|

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
SCV001396108	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 14, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 17932099, 22094069, 23739125, 22246887, 25487368, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001396108

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 14, 2023)

germline

clinical testing

PubMed (6)
[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

Chloride channel myotonia: exon 8 hot-spot for dominant-negative interactions.

Fialho D, Schorge S, Pucovska U, Davies NP, Labrum R, Haworth A, Stanley E, Sud R, Wakeling W, Davis MB, Kullmann DM, Hanna MG.

Brain. 2007 Dec;130(Pt 12):3265-74. Epub 2007 Oct 11.

PubMed [citation]

PMID:: 17932099

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 (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001396108.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change creates a premature translational stop signal (p.Lys248*) in the CLCN1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CLCN1 are known to be pathogenic (PMID: 17932099, 22094069, 23739125). This variant is present in population databases (rs561470261, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with autosomal recessive myotonia congenita (PMID: 22246887, 25487368). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 620142). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus 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: Oct 13, 2024

ClinVar

Relating variation to medicine