NM_001037.5(SCN1B):c.449-2A>G AND Developmental and epileptic encephalopathy, 52

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Mar 17, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000856658.6

Allele description [Variation Report for NM_001037.5(SCN1B):c.449-2A>G]

NM_001037.5(SCN1B):c.449-2A>G

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.449-2A>G

HGVS:

NC_000019.10:g.35039115A>G
NG_013359.1:g.13428A>G
NM_001037.5:c.449-2A>GMANE SELECT
NM_001321605.2:c.350-2A>G
LRG_420t1:c.449-2A>G
LRG_420:g.13428A>G
NC_000019.9:g.35530019A>G
NM_001037.4:c.449-2A>G

Nucleotide change:

IVS3AS, A-G, -2

Links:

OMIM: 600235.0010; dbSNP: rs1600370558

NCBI 1000 Genomes Browser:

rs1600370558

Molecular consequence:

NM_001037.5:c.449-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001321605.2:c.350-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

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
SCV000999199	OMIM	no assertion criteria provided	Pathogenic (Oct 9, 2020)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001520980	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 20, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004805071	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 17, 2024)	germline	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000999199

OMIM

no assertion criteria provided

Pathogenic
(Oct 9, 2020)

germline

literature only

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

SCV001520980

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Sep 20, 2019)

unknown

clinical testing

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

SCV004805071

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 17, 2024)

germline

research

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	research
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Confirming the recessive inheritance of SCN1B mutations in developmental epileptic encephalopathy.

Ramadan W, Patel N, Anazi S, Kentab AY, Bashiri FA, Hamad MH, Jad L, Salih MA, Alsaif H, Hashem M, Faqeih E, Shamseddin HE, Alkuraya FS.

Clin Genet. 2017 Sep;92(3):327-331. doi: 10.1111/cge.12999. Epub 2017 Apr 19.

PubMed [citation]

PMID:: 28218389

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 OMIM, SCV000999199.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 2 affected sibs in each of 2 consanguineous Saudi families (families 1 and 3) with developmental and epileptic encephalopathy-52 (DEE52; 617350), Ramadan et al. (2017) identified homozygosity for a splice site mutation (c.449-2A-G, NM_001037.4) in intron 3 of the SCN1B gene. The mutation, which was identified by sequencing of a multigene epilepsy panel and confirmed by Sanger sequencing, segregated with the disorder in the families. The variant was not found in the ExAC database or in over 7,000 Saudi controls. No functional studies were performed. The patients had onset of seizures in the first months of life; all died in the first decade of life.

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

From Baylor Genetics, SCV001520980.1

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

Description

This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].

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

From Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV004805071.2

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

#	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: Apr 6, 2024

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