ClinVar Genomic variation as it relates to human health
NM_001365536.1(SCN9A):c.2827A>C (p.Met943Leu)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001365536.1(SCN9A):c.2827A>C (p.Met943Leu)
Variation ID: 94089 Accession: VCV000094089.37
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q24.3 2: 166277030 (GRCh38) [ NCBI UCSC ] 2: 167133540 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jul 6, 2014 Feb 28, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001365536.1:c.2827A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001352465.1:p.Met943Leu missense NM_002977.4:c.2794A>C NP_002968.2:p.Met932Leu missense NC_000002.12:g.166277030T>G NC_000002.11:g.167133540T>G NG_012798.1:g.103958A>C LRG_369:g.103958A>C LRG_369t1:c.2794A>C LRG_369p1:p.Met932Leu - Protein change
- M943L
- Other names
- M932L
- Canonical SPDI
- NC_000002.12:166277029:T:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.03335 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00338
The Genome Aggregation Database (gnomAD) 0.01339
Trans-Omics for Precision Medicine (TOPMed) 0.02355
Exome Aggregation Consortium (ExAC) 0.02949
1000 Genomes Project 0.03335
1000 Genomes Project 30x 0.03435
The Genome Aggregation Database (gnomAD), exomes 0.03682
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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SCN1A-AS1 | - | - | - | GRCh38 | - | 2155 |
SCN9A | - | - |
GRCh38 GRCh37 |
439 | 2632 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Sep 25, 2013 | RCV000080038.29 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Mar 6, 2018 | RCV000399125.15 | |
Benign (1) |
criteria provided, single submitter
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Feb 1, 2024 | RCV000461431.17 | |
Likely benign (1) |
criteria provided, single submitter
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May 28, 2019 | RCV000986924.9 | |
Benign (3) |
criteria provided, multiple submitters, no conflicts
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Nov 2, 2023 | RCV000992914.21 | |
Benign (1) |
criteria provided, single submitter
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Mar 6, 2018 | RCV001129275.12 | |
Benign (1) |
criteria provided, single submitter
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Mar 6, 2018 | RCV001129274.12 | |
Uncertain risk allele (1) |
no assertion criteria provided
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Jul 28, 2023 | RCV003313935.8 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely benign
(-)
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criteria provided, single submitter
Method: clinical testing
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NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000309308.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
|
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Benign
(Sep 25, 2013)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000111932.8
First in ClinVar: Jan 17, 2014 Last updated: May 03, 2018 |
Number of individuals with the variant: 2
Sex: mixed
|
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Benign
(Dec 07, 2018)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Athena Diagnostics
Accession: SCV001145512.1
First in ClinVar: Jan 19, 2020 Last updated: Jan 19, 2020 |
|
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Benign
(Mar 06, 2018)
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criteria provided, single submitter
Method: clinical testing
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Primary erythromelalgia
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001288790.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Observation 1: Observation 2: |
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Benign
(Mar 06, 2018)
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criteria provided, single submitter
Method: clinical testing
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Paroxysmal extreme pain disorder
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001288789.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
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Benign
(Nov 21, 2018)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001839022.1
First in ClinVar: Sep 12, 2021 Last updated: Sep 12, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 27956748, 23895530, 25585270, 22803682, 25556685, 25250524, 21698661, 26284228, 27535533, 21939494, 23450472)
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Benign
(Nov 02, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001157148.6
First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024 |
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Likely benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Neuropathy, hereditary sensory and autonomic, type 2A
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001136080.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
|
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Benign
(Mar 06, 2018)
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criteria provided, single submitter
Method: clinical testing
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Channelopathy-associated congenital insensitivity to pain, autosomal recessive
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000418557.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
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Likely benign
(-)
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criteria provided, single submitter
Method: research
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Channelopathy-associated congenital insensitivity to pain, autosomal recessive
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV001435133.1
First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020 |
Comment:
The p.Met932Leu variant in SCN9A has been identified in at least 2 Chinese individuals with partial congenital indifference to pain (PMID: 21939494). This variant is … (more)
The p.Met932Leu variant in SCN9A has been identified in at least 2 Chinese individuals with partial congenital indifference to pain (PMID: 21939494). This variant is classified as likely benign for partial congenital indifference to pain because it has been identified in >23% of Latino chromosomes and 387 total homozygotes by ExAC (http://gnomad.broadinstitute.org/). (less)
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Neuropathy, hereditary sensory and autonomic, type 2A
Generalized epilepsy with febrile seizures plus, type 7
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000559256.7
First in ClinVar: Apr 17, 2017 Last updated: Feb 28, 2024 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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AllHighlyPenetrant
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000152670.2
First in ClinVar: May 17, 2014 Last updated: Jul 06, 2014 |
Comment:
Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated … (more)
Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. (less)
|
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Uncertain risk allele
(Jul 28, 2023)
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no assertion criteria provided
Method: clinical testing
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Autism spectrum disorder
Affected status: no, yes
Allele origin:
unknown
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Gene Friend Way, National Innovation Center
Accession: SCV004013893.2
First in ClinVar: Jul 22, 2023 Last updated: Aug 30, 2023 |
Comment:
Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated … (more)
Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. This variant and other mutations in SCN9A have been found in patients with familial autism (PMID: 27956748). In our study, about 10% of patients diagnosed with ASD carry this SCN9A variant. (less)
Observation 1:
Number of individuals with the variant: 20
Method: 800K direct targets snp array, validated with Sanger sequencing
Observation 2:
Number of individuals with the variant: 1
Comment on evidence:
Individual with ASD-like behavior
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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[Association between mutations of SCN9A gene and pain related to Parkinsonism]. | Zhang LM | Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics | 2013 | PMID: 23450472 |
Gain of function Naν1.7 mutations in idiopathic small fiber neuropathy. | Faber CG | Annals of neurology | 2012 | PMID: 21698661 |
Two novel SCN9A gene heterozygous mutations may cause partial deletion of pain perception. | Yuan R | Pain medicine (Malden, Mass.) | 2011 | PMID: 21939494 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SCN9A | - | - | - | - |
Text-mined citations for rs12478318 ...
HelpRecord last updated May 27, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.