NM_000083.3(CLCN1):c.920T>C (p.Phe307Ser) AND Congenital myotonia, autosomal recessive form

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 14, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV004562217.2

Allele description [Variation Report for NM_000083.3(CLCN1):c.920T>C (p.Phe307Ser)]

NM_000083.3(CLCN1):c.920T>C (p.Phe307Ser)

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.920T>C (p.Phe307Ser)

HGVS:

NC_000007.14:g.143330838T>C
NG_009815.2:g.19713T>C
NM_000083.3:c.920T>CMANE SELECT
NP_000074.3:p.Phe307Ser
NC_000007.13:g.143027931T>C
NG_009815.1:g.19713T>C
NM_000083.2:c.920T>C
NR_046453.2:n.1025T>C
P35523:p.Phe307Ser

Protein change:

F307S

Links:

UniProtKB: P35523#VAR_001598; dbSNP: rs80356701

NCBI 1000 Genomes Browser:

rs80356701

Molecular consequence:

NM_000083.3:c.920T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_046453.2:n.1025T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005049688	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 24, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005422319	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Oct 14, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 34529042, 23516313, 37273706, 15786415 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005049688

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 24, 2024)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV005422319

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Oct 14, 2024)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Translating genetic and functional data into clinical practice: a series of 223 families with myotonia.

Suetterlin K, Matthews E, Sud R, McCall S, Fialho D, Burge J, Jayaseelan D, Haworth A, Sweeney MG, Kullmann DM, Schorge S, Hanna MG, Männikkö R.

Brain. 2022 Apr 18;145(2):607-620. doi: 10.1093/brain/awab344.

PubMed [citation]

PMID:: 34529042
PMCID:: PMC9014745

See all PubMed Citations (5)

Details of each submission

From Baylor Genetics, SCV005049688.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005422319.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Variant summary: CLCN1 c.920T>C (p.Phe307Ser) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6e-05 in 251440 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in CLCN1 causing Myotonia congenita (6e-05 vs 0.0035), allowing no conclusion about variant significance. c.920T>C has been reported in the literature in the homozygous and compound heterozygous states in multiple individuals affected with Myotonia congenita (Horga_2013, Suetterlin_2022, Colding-Jorgensen_2003, Ek_2023). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 15786415, 37273706, 23516313, 34529042). ClinVar contains an entry for this variant (Variation ID: 21050). Based on the evidence outlined above, the variant was 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: Jan 13, 2025

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