NM_001365536.1(SCN9A):c.3430G>A (p.Glu1144Lys) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 2, 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:: RCV003813595.2

Allele description [Variation Report for NM_001365536.1(SCN9A):c.3430G>A (p.Glu1144Lys)]

NM_001365536.1(SCN9A):c.3430G>A (p.Glu1144Lys)

Genes:

SCN1A-AS1:SCN1A and SCN9A antisense RNA 1 [Gene - HGNC]
SCN9A:sodium voltage-gated channel alpha subunit 9 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q24.3

Genomic location:

Preferred name:

NM_001365536.1(SCN9A):c.3430G>A (p.Glu1144Lys)

HGVS:

NC_000002.12:g.166251807C>T
NG_012798.1:g.129181G>A
NM_001365536.1:c.3430G>AMANE SELECT
NM_002977.4:c.3397G>A
NP_001352465.1:p.Glu1144Lys
NP_002968.1:p.Glu1133Lys
NP_002968.1:p.Glu1133Lys
NP_002968.2:p.Glu1133Lys
LRG_369t1:c.3397G>A
LRG_369:g.129181G>A
LRG_369p1:p.Glu1133Lys
NC_000002.11:g.167108317C>T
NM_002977.2:c.3397G>A
NM_002977.3:c.3397G>A
NR_110260.1:n.764C>T

Protein change:

E1133K

Molecular consequence:

NM_001365536.1:c.3430G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002977.4:c.3397G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_110260.1:n.764C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Neuropathy, hereditary sensory and autonomic, type 2A (HSAN2A)
Synonyms:: ACROOSTEOLYSIS, GIACCAI TYPE; ACROOSTEOLYSIS, NEUROGENIC; HSAN IIA; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0024309; MedGen: C2752089; Orphanet: 970; OMIM: 201300

Name:: Generalized epilepsy with febrile seizures plus, type 7 (GEFSP7)
Synonyms:: GEFS+, TYPE 7
Identifiers:: MONDO: MONDO:0013470; MedGen: C2751778; Orphanet: 36387; OMIM: 613863

Recent activity

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PREDICTED: Homo sapiens disco interacting protein 2 homolog C (DIP2C), transcrip...
PREDICTED: Homo sapiens disco interacting protein 2 homolog C (DIP2C), transcript variant X10, mRNA
gi|2462517951|ref|XM_054365261.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004610623	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 2, 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

SCV004610623

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 2, 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	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004610623.1

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

Description

This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1133 of the SCN9A protein (p.Glu1133Lys). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with SCN9A-related conditions. 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) performed at Invitae indicates that this missense variant is not expected to disrupt SCN9A protein function with a negative predictive value of 95%. 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.

#	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

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