ClinVar Genomic variation as it relates to human health
NM_000454.5(SOD1):c.346C>G (p.Arg116Gly)
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_000454.5(SOD1):c.346C>G (p.Arg116Gly)
Variation ID: 805495 Accession: VCV000805495.25
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 21q22.11 21: 31667364 (GRCh38) [ NCBI UCSC ] 21: 33039677 (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 Jan 19, 2020 May 12, 2024 Oct 27, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000454.5:c.346C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000445.1:p.Arg116Gly missense NC_000021.9:g.31667364C>G NC_000021.8:g.33039677C>G NG_008689.1:g.12743C>G LRG_652:g.12743C>G LRG_652t1:c.346C>G - Protein change
- R116G
- Other names
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- Canonical SPDI
- NC_000021.9:31667363:C: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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Allele frequency
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The frequency of the allele represented by this VCV record.
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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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SOD1 | - | - |
GRCh38 GRCh37 |
200 | 312 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Oct 1, 2019 | RCV000993042.19 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Oct 27, 2022 | RCV002290508.4 |
Submissions - Germline
Classification
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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
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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
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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
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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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Pathogenic
(Aug 28, 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: SCV001145743.1
First in ClinVar: Jan 19, 2020 Last updated: Jan 19, 2020 |
Comment:
This variant is published to be a common German founder variant and has been published in over 23 ALS families. The best available variant frequency … (more)
This variant is published to be a common German founder variant and has been published in over 23 ALS families. The best available variant frequency is above the disease allele frequency but data include fewer than 10 observations. Statistically enriched in patients compared to ethnically matched controls. Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein. Statistically associated with disease in genotyped family members (p < 0.05), and data are from multiple families. (less)
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Likely pathogenic
(Jul 12, 2022)
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criteria provided, single submitter
Method: clinical testing
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Amyotrophic lateral sclerosis type 1
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002581167.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PS4_MOD, PM5, PS3_SUP, PM2_SUP, PP1, PP3
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Number of individuals with the variant: 1
Sex: female
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Pathogenic
(Oct 27, 2022)
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criteria provided, single submitter
Method: clinical testing
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Amyotrophic lateral sclerosis type 1
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV004297374.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects SOD1 function (PMID: 23280792). Advanced modeling … (more)
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects SOD1 function (PMID: 23280792). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SOD1 protein function. ClinVar contains an entry for this variant (Variation ID: 805495). This variant is also known as Arg115Gly. This missense change has been observed in individuals with amyotrophic lateral sclerosis (PMID: 7881433, 15258228). This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 116 of the SOD1 protein (p.Arg116Gly). (less)
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Pathogenic
(Oct 01, 2019)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001250467.21
First in ClinVar: May 12, 2020 Last updated: May 12, 2024 |
Number of individuals with the variant: 1
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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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Comprehensive analysis of the mutation spectrum in 301 German ALS families. | Müller K | Journal of neurology, neurosurgery, and psychiatry | 2018 | PMID: 29650794 |
Challenges in the Understanding and Treatment of Amyotrophic Lateral Sclerosis/Motor Neuron Disease. | Rosenfeld J | Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics | 2015 | PMID: 25572957 |
A novel monoclonal antibody reveals a conformational alteration shared by amyotrophic lateral sclerosis-linked SOD1 mutants. | Fujisawa T | Annals of neurology | 2012 | PMID: 23280792 |
The epidemiology of CuZn-SOD mutations in Germany: a study of 217 families. | Rabe M | Journal of neurology | 2010 | PMID: 20309572 |
Superoxide dismutase from the eukaryotic thermophile Alvinella pompejana: structures, stability, mechanism, and insights into amyotrophic lateral sclerosis. | Shin DS | Journal of molecular biology | 2009 | PMID: 19063897 |
Amyotrophic lateral sclerosis-associated copper/zinc superoxide dismutase mutations preferentially reduce the repulsive charge of the proteins. | Sandelin E | The Journal of biological chemistry | 2007 | PMID: 17513298 |
Rapid disease progression correlates with instability of mutant SOD1 in familial ALS. | Sato T | Neurology | 2005 | PMID: 16291929 |
Familial ALS in Germany: origin of the R115G SOD1 mutation by a founder effect. | Niemann S | Journal of neurology, neurosurgery, and psychiatry | 2004 | PMID: 15258228 |
Folding of Cu, Zn superoxide dismutase and familial amyotrophic lateral sclerosis. | Khare SD | Journal of molecular biology | 2003 | PMID: 14623191 |
Sixteen novel mutations in the Cu/Zn superoxide dismutase gene in amyotrophic lateral sclerosis: a decade of discoveries, defects and disputes. | Andersen PM | Amyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases | 2003 | PMID: 14506936 |
Autosomal dominant amyotrophic lateral sclerosis: a novel mutation in the Cu/Zn superoxide dismutase-1 gene. | Kostrzewa M | Human molecular genetics | 1994 | PMID: 7881433 |
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Text-mined citations for rs1301635320 ...
HelpRecord last updated May 12, 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.