NM_001365536.1(SCN9A):c.4892G>T (p.Arg1631Leu) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: May 28, 2020
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000489681.7

Allele description [Variation Report for NM_001365536.1(SCN9A):c.4892G>T (p.Arg1631Leu)]

NM_001365536.1(SCN9A):c.4892G>T (p.Arg1631Leu)

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.4892G>T (p.Arg1631Leu)

HGVS:

NC_000002.12:g.166199747C>A
NG_012798.1:g.181241G>T
NM_001365536.1:c.4892G>TMANE SELECT
NM_002977.4:c.4859G>T
NP_001352465.1:p.Arg1631Leu
NP_002968.1:p.Arg1620Leu
NP_002968.1:p.Arg1620Leu
NP_002968.2:p.Arg1620Leu
LRG_369t1:c.4859G>T
LRG_369:g.181241G>T
LRG_369p1:p.Arg1620Leu
NC_000002.11:g.167056257C>A
NM_002977.2:c.4859G>T
NM_002977.3:c.4859G>T
NR_110260.1:n.540C>A
p.Arg1620Leu

Protein change:

R1620L

Links:

dbSNP: rs201079869

NCBI 1000 Genomes Browser:

rs201079869

Molecular consequence:

NM_001365536.1:c.4892G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002977.4:c.4859G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_110260.1:n.540C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000577333	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Dec 12, 2018)	germline	clinical testing	Citation Link,
SCV001714615	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 28, 2020)	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

SCV000577333

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Dec 12, 2018)

germline

clinical testing

Citation Link,

SCV001714615

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 28, 2020)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000577333.4

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

Description

A variant of uncertain significance has been identified in the SCN9A gene. The R1620L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R1620L variant is observed in 4/66,740 alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R1620L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a conserved position predicted to be within the transmembrance segment S4 voltage sensor of the fourth homologous domain. In silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV001714615.1

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

#	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		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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