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NM_001330260.2(SCN8A):c.5087T>G (p.Ile1696Ser) AND Developmental and epileptic encephalopathy, 13

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 17, 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:
RCV002471629.2

Allele description [Variation Report for NM_001330260.2(SCN8A):c.5087T>G (p.Ile1696Ser)]

NM_001330260.2(SCN8A):c.5087T>G (p.Ile1696Ser)

Gene:
SCN8A:sodium voltage-gated channel alpha subunit 8 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q13.13
Genomic location:
Preferred name:
NM_001330260.2(SCN8A):c.5087T>G (p.Ile1696Ser)
HGVS:
  • NC_000012.12:g.51806573T>G
  • NG_021180.3:g.221616T>G
  • NM_001177984.3:c.4964T>G
  • NM_001330260.2:c.5087T>GMANE SELECT
  • NM_001369788.1:c.4964T>G
  • NM_014191.4:c.5087T>G
  • NP_001171455.1:p.Ile1655Ser
  • NP_001317189.1:p.Ile1696Ser
  • NP_001356717.1:p.Ile1655Ser
  • NP_055006.1:p.Ile1696Ser
  • LRG_1389t1:c.5087T>G
  • LRG_1389t2:c.5087T>G
  • LRG_1389:g.221616T>G
  • LRG_1389p1:p.Ile1696Ser
  • LRG_1389p2:p.Ile1696Ser
  • NC_000012.11:g.52200357T>G
  • NM_001330260.1:c.5087T>G
Protein change:
I1655S
Molecular consequence:
  • NM_001177984.3:c.4964T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330260.2:c.5087T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369788.1:c.4964T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014191.4:c.5087T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Developmental and epileptic encephalopathy, 13 (DEE13)
Synonyms:
Early infantile epileptic encephalopathy 13; SCN8A-Related Epilepsy
Identifiers:
MONDO: MONDO:0013801; MedGen: C3281191; Orphanet: 442835; OMIM: 614558

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002769034Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Jul 17, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Phenotypic and genetic spectrum of SCN8A-related disorders, treatment options, and outcomes.

Gardella E, Møller RS.

Epilepsia. 2019 Dec;60 Suppl 3:S77-S85. doi: 10.1111/epi.16319.

PubMed [citation]
PMID:
31904124

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 Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002769034.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0103 - Loss of function and gain of function are known mechanisms of disease in this gene, and are associated with cognitive impairment with or without cerebellar ataxia (MIM#614306), and developmental and epileptic encephalopathy 13 (MIM#614558), respectively. In addition, gain of function is speculated for benign familial infantile seizures, 5 (MIM#617080) (PMID: 31904124, OMIM). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from isoleucine to serine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0603 - Missense variant in a region that is highly intolerant to missense variation (high constraint region in DECIPHER). (SP) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0904 - Non-segregation of this variant with the phenotype under investigation has been clearly demonstrated. It has been found in unaffected heterozygous relatives. (SB) 1007 - No published functional evidence has been identified for this variant. (I) 1205 - This variant has been shown to be maternally inherited. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 29, 2024