NM_001349253.2(SCN11A):c.1576G>C (p.Val526Leu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 16, 2022
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:: RCV000820984.4

Allele description [Variation Report for NM_001349253.2(SCN11A):c.1576G>C (p.Val526Leu)]

NM_001349253.2(SCN11A):c.1576G>C (p.Val526Leu)

Gene:

SCN11A:sodium voltage-gated channel alpha subunit 11 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_001349253.2(SCN11A):c.1576G>C (p.Val526Leu)

HGVS:

NC_000003.12:g.38905219C>G
NG_033859.2:g.151768G>C
NM_001349253.2:c.1576G>CMANE SELECT
NM_014139.3:c.1576G>C
NP_001336182.1:p.Val526Leu
NP_054858.2:p.Val526Leu
NP_054858.2:p.Val526Leu
NC_000003.11:g.38946710C>G
NM_014139.2:c.1576G>C

Protein change:

V526L

Links:

dbSNP: rs201958340

NCBI 1000 Genomes Browser:

rs201958340

Molecular consequence:

NM_001349253.2:c.1576G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_014139.3:c.1576G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary sensory and autonomic neuropathy type 7
Synonyms:: HSAN VII; Neuropathy, hereditary sensory and autonomic, type VII
Identifiers:: MONDO: MONDO:0014244; MedGen: C3809882; Orphanet: 391397; OMIM: 615548

Name:: Familial episodic pain syndrome with predominantly lower limb involvement
Synonyms:: Episodic pain syndrome, familial, 3
Identifiers:: MONDO: MONDO:0014247; MedGen: C3809899; Orphanet: 391384; Orphanet: 391392; OMIM: 615552

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000961723	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 16, 2022)	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

SCV000961723

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 16, 2022)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000961723.5

#	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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 663163). This variant has not been reported in the literature in individuals affected with SCN11A-related conditions. This variant is present in population databases (rs201958340, gnomAD 0.0009%). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 526 of the SCN11A protein (p.Val526Leu).

#	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: Feb 28, 2024

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