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NM_000083.3(CLCN1):c.434-2_434dup AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 10, 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:
RCV000550058.8

Allele description [Variation Report for NM_000083.3(CLCN1):c.434-2_434dup]

NM_000083.3(CLCN1):c.434-2_434dup

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.434-2_434dup
HGVS:
  • NC_000007.14:g.143321363_143321365dup
  • NG_009815.2:g.10238_10240dup
  • NM_000083.3:c.434-2_434dupMANE SELECT
  • NC_000007.13:g.143018453_143018454insGCA
  • NC_000007.13:g.143018456_143018458dup
  • NG_009815.1:g.10238_10240dup
  • NM_000083.2:c.434-2_434dup
  • NM_000083.2:c.434-2_434dupAGC
  • NM_000083.3:c.434-2_434dupAGCMANE SELECT
  • NM_000083.3:c.434_435insAGCMANE SELECT
Links:
dbSNP: rs753470655
NCBI 1000 Genomes Browser:
rs753470655
Molecular consequence:
  • NM_000083.3:c.434-2_434dup - splice acceptor variant - [Sequence Ontology: SO:0001574]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000636331Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 10, 2024) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Myotonia congenita: mutation spectrum of CLCN1 in Spanish patients.

Milla CP, De Castro CP, Gómez-González C, Martínez-Montero P, Pascual Pascual SI, Molano Mateos J.

J Genet. 2019 Sep;98. doi:pii: 71.

PubMed [citation]
PMID:
31544778

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000636331.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This variant, c.434-2_434dup, results in the insertion of 1 amino acid(s) of the CLCN1 protein (p.Ala145dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs753470655, gnomAD 0.007%). This variant has been observed in individual(s) with clinical features of autosomal recessive myotonia congenita (PMID: 31544778; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant has been reported in individual(s) with autosomal dominant myotonia congenita (PMID: 31544778); however, the role of the variant in this condition is currently unclear. This variant is also known as c.434-5_434-4insGCA. ClinVar contains an entry for this variant (Variation ID: 462844). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024