NM_000083.3(CLCN1):c.1727C>T (p.Ser576Phe) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 13, 2022
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:: RCV001926699.4

Allele description [Variation Report for NM_000083.3(CLCN1):c.1727C>T (p.Ser576Phe)]

NM_000083.3(CLCN1):c.1727C>T (p.Ser576Phe)

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.1727C>T (p.Ser576Phe)

HGVS:

NC_000007.14:g.143342073C>T
NG_009815.2:g.30948C>T
NM_000083.3:c.1727C>TMANE SELECT
NP_000074.3:p.Ser576Phe
NC_000007.13:g.143039166C>T
NG_009815.1:g.30948C>T
NR_046453.2:n.1682C>T

Protein change:

S576F

Links:

dbSNP: rs143825889

NCBI 1000 Genomes Browser:

rs143825889

Molecular consequence:

NM_000083.3:c.1727C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_046453.2:n.1682C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

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IRF4 contributes to chemoresistance in IGH-BCL2 positive diffuse large B-cell lymphomas by mediating BCL2 induced SOX9 expression
IRF4 contributes to chemoresistance in IGH-BCL2 positive diffuse large B-cell lymphomas by mediating BCL2 induced SOX9 expression

BioProject
Orchomenella pinguides voucher RBINS:CDB OP-WS387 28S ribosomal RNA gene, partia...
Orchomenella pinguides voucher RBINS:CDB OP-WS387 28S ribosomal RNA gene, partial sequence
gi|282722431|gb|GU109215.1|

Nucleotide
COX1 [Blepharipoda liberata]
COX1 [Blepharipoda liberata]
Gene ID:74863601

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002206126	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 13, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002206126

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 13, 2022)

germline

clinical testing

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

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

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, SCV002206126.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CLCN1 protein function. ClinVar contains an entry for this variant (Variation ID: 1425513). This variant has not been reported in the literature in individuals affected with CLCN1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 576 of the CLCN1 protein (p.Ser576Phe).

#	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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