NM_005097.4(LGI1):c.136T>C (p.Cys46Arg) AND Autosomal dominant epilepsy with auditory features

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 28, 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:: RCV003595853.2

Allele description [Variation Report for NM_005097.4(LGI1):c.136T>C (p.Cys46Arg)]

NM_005097.4(LGI1):c.136T>C (p.Cys46Arg)

Gene:

LGI1:leucine rich glioma inactivated 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q23.33

Genomic location:

Preferred name:

NM_005097.4(LGI1):c.136T>C (p.Cys46Arg)

HGVS:

NC_000010.11:g.93758280T>C
NG_011832.1:g.5472T>C
NM_001308275.2:c.136T>C
NM_001308276.2:c.136T>C
NM_005097.4:c.136T>CMANE SELECT
NP_001295204.1:p.Cys46Arg
NP_001295205.1:p.Cys46Arg
NP_005088.1:p.Cys46Arg
NC_000010.10:g.95518037T>C
NM_005097.2:c.136T>C
NR_131777.2:n.345T>C
O95970:p.Cys46Arg

Protein change:

C46R; CYS46ARG

Links:

UniProtKB: O95970#VAR_015772; OMIM: 604619.0004; dbSNP: rs104894166

NCBI 1000 Genomes Browser:

rs104894166

Molecular consequence:

NM_001308275.2:c.136T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001308276.2:c.136T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_005097.4:c.136T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_131777.2:n.345T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Autosomal dominant epilepsy with auditory features
Identifiers:: MONDO: MONDO:0010898; MedGen: C1838062

Recent activity

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ribose ABC transporter [Paraburkholderia acidiphila]
ribose ABC transporter [Paraburkholderia acidiphila]
gi|1787165844|gnl|PRJNA534068|FAZ97 0|gb|QGZ59861.1|

Protein
ST47ORF013 [Staphylococcus phage 47]
ST47ORF013 [Staphylococcus phage 47]
Gene ID:5133055

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004295658	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 28, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 17067999, 25485908, 12205652, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004295658

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 28, 2022)

germline

clinical testing

PubMed (4)
[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

The epilepsy gene LGI1 encodes a secreted glycoprotein that binds to the cell surface.

Sirerol-Piquer MS, Ayerdi-Izquierdo A, Morante-Redolat JM, Herranz-Pérez V, Favell K, Barker PA, Pérez-Tur J.

Hum Mol Genet. 2006 Dec 1;15(23):3436-45. Epub 2006 Oct 26.

PubMed [citation]

PMID:: 17067999

Chemical corrector treatment ameliorates increased seizure susceptibility in a mouse model of familial epilepsy.

Yokoi N, Fukata Y, Kase D, Miyazaki T, Jaegle M, Ohkawa T, Takahashi N, Iwanari H, Mochizuki Y, Hamakubo T, Imoto K, Meijer D, Watanabe M, Fukata M.

Nat Med. 2015 Jan;21(1):19-26. doi: 10.1038/nm.3759. Epub 2014 Dec 8.

PubMed [citation]

PMID:: 25485908

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004295658.1

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

Description

Experimental studies have shown that this missense change affects LGI1 function (PMID: 17067999, 25485908). For these reasons, this variant has been classified as Pathogenic. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on LGI1 protein function. ClinVar contains an entry for this variant (Variation ID: 5433). This missense change has been observed in individual(s) with autosomal dominant lateral temporal lobe epilepsy (PMID: 12205652). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 46 of the LGI1 protein (p.Cys46Arg).

#	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

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