NM_001365536.1(SCN9A):c.1286_1287delinsAA (p.Arg429Gln) 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:: RCV002525995.4

Allele description [Variation Report for NM_001365536.1(SCN9A):c.1286_1287delinsAA (p.Arg429Gln)]

NM_001365536.1(SCN9A):c.1286_1287delinsAA (p.Arg429Gln)

Genes:

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

Variant type:

Indel

Cytogenetic location:

2q24.3

Genomic location:

Preferred name:

NM_001365536.1(SCN9A):c.1286_1287delinsAA (p.Arg429Gln)

HGVS:

NC_000002.12:g.166288464_166288465delinsTT
NG_012798.1:g.92523_92524delinsAA
NM_001365536.1:c.1286_1287delinsAAMANE SELECT
NM_002977.4:c.1286_1287delGTinsAA
NP_001352465.1:p.Arg429Gln
NP_002968.1:p.Arg429Gln
NP_002968.1:p.Arg429Gln
NP_002968.2:p.Arg429Gln
LRG_369t1:c.1286_1287delinsAA
LRG_369:g.92523_92524delinsAA
LRG_369p1:p.Arg429Gln
NC_000002.11:g.167144974_167144975delinsTT
NM_002977.2:c.1286_1287delGTinsAA
NM_002977.3:c.1286_1287delinsAA

Protein change:

R429Q

Links:

dbSNP: rs1064797268

NCBI 1000 Genomes Browser:

rs1064797268

Molecular consequence:

NM_001365536.1:c.1286_1287delinsAA - missense variant - [Sequence Ontology: SO:0001583]
NM_002977.4:c.1286_1287delGTinsAA - missense variant - [Sequence Ontology: SO:0001583]

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

Clear Turn Off Turn On

Membrane protein, palmitoylated 4 (MAGUK p55 subfamily member 4) [Mus musculus]
Membrane protein, palmitoylated 4 (MAGUK p55 subfamily member 4) [Mus musculus]
gi|133777068|gb|AAH61694.2|

Protein

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
SCV003293476	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

SCV003293476

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, SCV003293476.2

#	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 arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 429 of the SCN9A protein (p.Arg429Gln). This variant is present in population databases (no rsID available, gnomAD 0.001%). This variant has not been reported in the literature in individuals affected with SCN9A-related conditions. ClinVar contains an entry for this variant (Variation ID: 425231). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. 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

ClinVar

Relating variation to medicine