NM_001365536.1(SCN9A):c.4141C>T (p.Arg1381Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 22, 2021
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:: RCV003060468.3

Allele description [Variation Report for NM_001365536.1(SCN9A):c.4141C>T (p.Arg1381Ter)]

NM_001365536.1(SCN9A):c.4141C>T (p.Arg1381Ter)

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.4141C>T (p.Arg1381Ter)

HGVS:

NC_000002.12:g.166228756G>A
NG_012798.1:g.152232C>T
NM_001365536.1:c.4141C>TMANE SELECT
NM_002977.4:c.4108C>T
NP_001352465.1:p.Arg1381Ter
NP_002968.1:p.Arg1370Ter
NP_002968.1:p.Arg1370Ter
NP_002968.2:p.Arg1370Ter
LRG_369t1:c.4108C>T
LRG_369:g.152232C>T
LRG_369p1:p.Arg1370Ter
NC_000002.11:g.167085266G>A
NM_002977.2:c.4108C>T
NM_002977.3:c.4108C>T

Protein change:

R1370*

Molecular consequence:

NM_001365536.1:c.4141C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_002977.4:c.4108C>T - nonsense - [Sequence Ontology: SO:0001587]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003448885	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 22, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17470132, 19304393, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003448885

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 22, 2021)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Loss-of-function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations.

Goldberg YP, MacFarlane J, MacDonald ML, Thompson J, Dube MP, Mattice M, Fraser R, Young C, Hossain S, Pape T, Payne B, Radomski C, Donaldson G, Ives E, Cox J, Younghusband HB, Green R, Duff A, Boltshauser E, Grinspan GA, Dimon JH, Sibley BG, et al.

Clin Genet. 2007 Apr;71(4):311-9.

PubMed [citation]

PMID:: 17470132

Two novel SCN9A mutations causing insensitivity to pain.

Nilsen KB, Nicholas AK, Woods CG, Mellgren SI, Nebuchennykh M, Aasly J.

Pain. 2009 May;143(1-2):155-8. doi: 10.1016/j.pain.2009.02.016. Epub 2009 Mar 21. Erratum in: Pain. 2009 Sep;145(1-2):264.

PubMed [citation]

PMID:: 19304393

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003448885.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with SCN9A-related conditions. This variant is present in population databases (rs748159444, gnomAD 0.02%). This sequence change creates a premature translational stop signal (p.Arg1370*) in the SCN9A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SCN9A are known to be pathogenic (PMID: 17470132, 19304393).

#	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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