NM_001330260.2(SCN8A):c.2533T>C (p.Ser845Pro) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 28, 2016
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:: RCV000413870.1

Allele description [Variation Report for NM_001330260.2(SCN8A):c.2533T>C (p.Ser845Pro)]

NM_001330260.2(SCN8A):c.2533T>C (p.Ser845Pro)

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.2533T>C (p.Ser845Pro)

HGVS:

NC_000012.12:g.51762665T>C
NG_021180.3:g.177708T>C
NM_001177984.3:c.2533T>C
NM_001330260.2:c.2533T>CMANE SELECT
NM_001369788.1:c.2533T>C
NM_014191.4:c.2533T>C
NP_001171455.1:p.Ser845Pro
NP_001317189.1:p.Ser845Pro
NP_001356717.1:p.Ser845Pro
NP_055006.1:p.Ser845Pro
LRG_1389t1:c.2533T>C
LRG_1389t2:c.2533T>C
LRG_1389:g.177708T>C
LRG_1389p1:p.Ser845Pro
LRG_1389p2:p.Ser845Pro
NC_000012.11:g.52156449T>C
NM_014191.3:c.2533T>C

Protein change:

S845P

Links:

dbSNP: rs1057518356

NCBI 1000 Genomes Browser:

rs1057518356

Molecular consequence:

NM_001177984.3:c.2533T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001330260.2:c.2533T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001369788.1:c.2533T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_014191.4:c.2533T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: CN517202

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Tom34p [Saccharomyces cerevisiae]
Tom34p [Saccharomyces cerevisiae]
gi|495308|gb|AAA64803.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000491919	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Likely pathogenic (Nov 28, 2016)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000491919

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Likely pathogenic
(Nov 28, 2016)

germline

clinical testing

Citation Link

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

Details of each submission

From GeneDx, SCV000491919.1

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

Description

A novel variant that is likely pathogenic has been identified in the SCN8A gene. The S845P variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S845P variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a conserved position within the transmembrane segment S4 voltage sensor of the second homologous domain. Missense variants in nearby residues (F846S and R850Q) have been reported in the Human Gene Mutation Database in association with SCN8A-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Additionally, in silico analysis predicts the S845P variant is probably damaging to the protein structure/function. Therefore, this variant is 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: Sep 17, 2022

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