VCV001000049.12 - ClinVar

NM_001040142.2(SCN2A):c.4901G>T (p.Gly1634Val)

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Pathogenic
Pathogenic (1)

1 out of 2 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001040142.2(SCN2A):c.4901G>T (p.Gly1634Val)

Variation ID: 1000049 Accession: VCV001000049.12

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2q24.3 2: 165388707 (GRCh38) [ NCBI UCSC ] 2: 166245217 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Mar 7, 2021	Feb 23, 2026	Jun 27, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_001040142.2:c.4901G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001035232.1:p.Gly1634Val	missense
NM_001371246.1:c.4901G>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001358175.1:p.Gly1634Val	missense
NM_001040143.2:c.4901G>T	NP_001035233.1:p.Gly1634Val	missense
NM_001371247.1:c.4901G>T	NP_001358176.1:p.Gly1634Val	missense
NM_021007.3:c.4901G>T	NP_066287.2:p.Gly1634Val	missense
NC_000002.12:g.165388707G>T
NC_000002.11:g.166245217G>T
NG_008143.1:g.154306G>T

... more HGVS ... less HGVS

Protein change

G1634V

Other names

Canonical SPDI

NC_000002.12:165388706:G:T

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA349037754 dbSNP: rs1553463427 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
SCN2A		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	3022	3099

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Developmental and epileptic encephalopathy, 11 Seizures, benign familial infantile, 3	Pathogenic (1)	criteria provided, single submitter	Jun 27, 2022	RCV001296127.9
Epilepsy of infancy with migrating focal seizures	Pathogenic (1)	no assertion criteria provided	Feb 16, 2022	RCV001847232.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Jun 27, 2022) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Seizures, benign familial infantile, 3 Developmental and epileptic encephalopathy, 11 Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001485083.6 First in ClinVar: Mar 07, 2021 Last updated: Feb 23, 2026	Publications: PubMed (1) PubMed: 27328862 Comment: show Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly1634 amino acid residue in SCN2A. Other variant(s) that disrupt this residue have been observed in individuals with SCN2A-related conditions (PMID: 27328862), which suggests that this may be a clinically significant amino acid residue. ClinVar contains an entry for this variant (Variation ID: 1000049). This missense change has been observed in individual(s) with SCN2A-related conditions (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1634 of the SCN2A protein (p.Gly1634Val). (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Feb 16, 2022) N Not contributing to aggregate classification	no assertion criteria provided	Epilepsy of infancy with migrating focal seizures	Neurology Department, Shenzhen Children's Hospital Accession: SCV002099502.1 First in ClinVar: Mar 19, 2022 Last updated: Mar 19, 2022	Observation: 1 Collection method: clinical testing Allele origin: de novo Affected status: yes Observation 1 Collection method: clinical testing Allele origin: de novo Affected status: yes

Comment:

Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly1634 amino acid residue in SCN2A. Other variant(s) that disrupt this residue have been observed in individuals with SCN2A-related conditions (PMID: 27328862), which suggests that this may be a clinically significant amino acid residue. ClinVar contains an entry for this variant (Variation ID: 1000049). This missense change has been observed in individual(s) with SCN2A-related conditions (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1634 of the SCN2A protein (p.Gly1634Val).

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Episodic ataxia associated with a de novo SCN2A mutation.	Leach EL	European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society	2016	PMID: 27328862

Text-mined citations for rs1553463427 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jun 14, 2026