NM_001365536.1(SCN9A):c.4156A>C (p.Lys1386Gln) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Dec 27, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001041147.2

Allele description [Variation Report for NM_001365536.1(SCN9A):c.4156A>C (p.Lys1386Gln)]

NM_001365536.1(SCN9A):c.4156A>C (p.Lys1386Gln)

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.4156A>C (p.Lys1386Gln)
HGVS:
  • NC_000002.12:g.166228741T>G
  • NG_012798.1:g.152247A>C
  • NM_001365536.1:c.4156A>CMANE SELECT
  • NM_002977.3:c.4123A>C
  • NP_001352465.1:p.Lys1386Gln
  • NP_002968.1:p.Lys1375Gln
  • LRG_369t1:c.4123A>C
  • LRG_369:g.152247A>C
  • LRG_369p1:p.Lys1375Gln
  • NC_000002.11:g.167085251T>G
Protein change:
K1375Q
Links:
dbSNP: rs199902747
NCBI 1000 Genomes Browser:
rs199902747
Molecular consequence:
  • NM_001365536.1:c.4156A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002977.3:c.4123A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary sensory and autonomic neuropathy type IIA (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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001204747Invitaecriteria provided, single submitter
Uncertain significance
(Dec 27, 2019)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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, SCV001204747.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces lysine with glutamine at codon 1375 of the SCN9A protein (p.Lys1375Gln). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamine. This variant is present in population databases (rs199902747, ExAC 0.002%). This variant has not been reported in the literature in individuals with SCN9A-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 7, 2021

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