NM_001037.5(SCN1B):c.253C>T (p.Arg85Cys) AND Developmental and epileptic encephalopathy, 52

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 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:: RCV003448275.2

Allele description [Variation Report for NM_001037.5(SCN1B):c.253C>T (p.Arg85Cys)]

NM_001037.5(SCN1B):c.253C>T (p.Arg85Cys)

Gene:

SCN1B:sodium voltage-gated channel beta subunit 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19q13.11

Genomic location:

Preferred name:

NM_001037.5(SCN1B):c.253C>T (p.Arg85Cys)

HGVS:

NC_000019.10:g.35033544C>T
NG_013359.1:g.7857C>T
NM_001037.5:c.253C>TMANE SELECT
NM_001321605.2:c.154C>T
NM_199037.5:c.253C>T
NP_001028.1:p.Arg85Cys
NP_001308534.1:p.Arg52Cys
NP_950238.1:p.Arg85Cys
LRG_420t1:c.253C>T
LRG_420:g.7857C>T
LRG_420p1:p.Arg85Cys
NC_000019.9:g.35524448C>T
NM_001037.4:c.253C>T
NM_199037.3:c.253C>T

Protein change:

R52C

Links:

dbSNP: rs786205830

NCBI 1000 Genomes Browser:

rs786205830

Molecular consequence:

NM_001037.5:c.253C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001321605.2:c.154C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_199037.5:c.253C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Developmental and epileptic encephalopathy, 52 (DEE52)
Synonyms:: Epileptic encephalopathy, early infantile, 52
Identifiers:: MONDO: MONDO:0033361; MedGen: C4479236; OMIM: 617350

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004176455	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 14, 2023)	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

SCV004176455

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 14, 2023)

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	yes	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

Details of each submission

From Neuberg Centre For Genomic Medicine, NCGM, SCV004176455.1

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

Description

The missense c.253C>T(p.Arg85Cys) variant in SCN1B gene has been reported in heterozygous state in multiple individuals affected with SCN1B related disorders (Aeby A, et. al., 2019). Experimental studies have shown that this missense change affects SCN1B function (Xu R, et. al., 2007). The p.Arg85Cys variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Uncertain Significance/Pathogenic/Likely pathogenic. The amino acid change p.Arg85Cys in SCN1B is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Arg at position 85 is changed to a Cys changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Likely Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 1, 2024

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