NM_006922.4(SCN3A):c.3986T>G (p.Val1329Gly) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 22, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001765405.4

Allele description [Variation Report for NM_006922.4(SCN3A):c.3986T>G (p.Val1329Gly)]

NM_006922.4(SCN3A):c.3986T>G (p.Val1329Gly)

Gene:

SCN3A:sodium voltage-gated channel alpha subunit 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q24.3

Genomic location:

Preferred name:

NM_006922.4(SCN3A):c.3986T>G (p.Val1329Gly)

HGVS:

NC_000002.12:g.165097505A>C
NG_042289.1:g.111584T>G
NM_001081676.2:c.3839T>G
NM_001081677.2:c.3839T>G
NM_006922.4:c.3986T>GMANE SELECT
NP_001075145.1:p.Val1280Gly
NP_001075146.1:p.Val1280Gly
NP_008853.3:p.Val1329Gly
NC_000002.11:g.165954015A>C
NM_006922.3:c.3986T>G

Protein change:

V1280G

Links:

dbSNP: rs1685414246

NCBI 1000 Genomes Browser:

rs1685414246

Molecular consequence:

NM_001081676.2:c.3839T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001081677.2:c.3839T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006922.4:c.3986T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

zinc finger protein 850-like [Geotrypetes seraphini]
zinc finger protein 850-like [Geotrypetes seraphini]
gi|1835638629|ref|XP_033788416.1|

Protein
SRX20546163 (1)
SRA
PREDICTED: Homo sapiens butyrophilin like 9 (BTNL9), transcript variant X4, mRNA
PREDICTED: Homo sapiens butyrophilin like 9 (BTNL9), transcript variant X4, mRNA
gi|2462600915|ref|XM_054351807.1|

Nucleotide
protein 4.1 isoform X35 [Homo sapiens]
protein 4.1 isoform X35 [Homo sapiens]
gi|2462505918|ref|XP_054190994.1|

Protein
DB339610 TESTI4 Homo sapiens cDNA clone TESTI4005911 3', mRNA sequence
DB339610 TESTI4 Homo sapiens cDNA clone TESTI4005911 3', mRNA sequence
gi|83175650|gnl|dbEST|34290935|dbj| 610.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001998077	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Oct 14, 2019)	germline	clinical testing	Citation Link,
SCV004667541	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 22, 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

SCV001998077

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Oct 14, 2019)

germline

clinical testing

Citation Link,

SCV004667541

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 22, 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
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From GeneDx, SCV001998077.2

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

Description

Not observed In large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004667541.1

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SCN3A protein function. ClinVar contains an entry for this variant (Variation ID: 1309236). This variant has not been reported in the literature in individuals affected with SCN3A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 1329 of the SCN3A protein (p.Val1329Gly).

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine