ClinVar Genomic variation as it relates to human health
NM_000454.5(SOD1):c.125G>A (p.Gly42Asp)
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.125G>A (p.Gly42Asp)
Variation ID: 14755 Accession: VCV000014755.5
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 21q22.11 21: 31663842 (GRCh38) [ NCBI UCSC ] 21: 33036155 (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 Apr 30, 2016 Feb 14, 2024 Jul 24, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000454.5:c.125G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000445.1:p.Gly42Asp missense NC_000021.9:g.31663842G>A NC_000021.8:g.33036155G>A NG_008689.1:g.9221G>A LRG_652:g.9221G>A LRG_652t1:c.125G>A LRG_652p1:p.Gly42Asp P00441:p.Gly42Asp - Protein change
- G42D
- Other names
- G41D
- Canonical SPDI
- NC_000021.9:31663841:G:A
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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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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 | 313 |
Conditions - Germline
Condition
Help
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 (3) |
criteria provided, multiple submitters, no conflicts
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Jul 24, 2023 | RCV000015877.30 |
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
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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
(Jun 26, 2023)
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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: SCV000766155.4
First in ClinVar: Apr 30, 2016 Last updated: Feb 14, 2024 |
Comment:
This missense change has been observed in individuals with autosomal dominant amyotrophic lateral sclerosis (PMID: 8446170, 9029070, 16291929, 16793335, 26069299, 28291249). It has also been … (more)
This missense change has been observed in individuals with autosomal dominant amyotrophic lateral sclerosis (PMID: 8446170, 9029070, 16291929, 16793335, 26069299, 28291249). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 42 of the SOD1 protein (p.Gly42Asp). This variant is also known as Gly41Asp. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects SOD1 function (PMID: 7891072, 19483195, 20404329, 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: 14755). (less)
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Pathogenic
(Jul 24, 2023)
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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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Human Genetics Bochum, Ruhr University Bochum
Accession: SCV004042805.1
First in ClinVar: Oct 21, 2023 Last updated: Oct 21, 2023 |
Comment:
ACMG criteria used to clasify this variant:PS4, PS3_MOD, PP3_MOD, PM2_SUP, PP1
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Pathogenic
(Apr 01, 1995)
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no assertion criteria provided
Method: literature only
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AMYOTROPHIC LATERAL SCLEROSIS 1
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000036144.2
First in ClinVar: Apr 04, 2013 Last updated: Apr 30, 2016 |
Comment on evidence:
In affected members of a family with autosomal dominant amyotrophic lateral sclerosis (105400), Rosen et al. (1993) identified a heterozygous G-to-A transition in exon 2 … (more)
In affected members of a family with autosomal dominant amyotrophic lateral sclerosis (105400), Rosen et al. (1993) identified a heterozygous G-to-A transition in exon 2 of the SOD1 gene, resulting in a gly41-to-asp (G41D) substitution. In a baculovirus expression system in insect cells, Fujii et al. (1995) found that the G41D enzyme exhibited 47% of wildtype SOD1 activity. (less)
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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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Analysis of SOD1 mutations in a Chinese population with amyotrophic lateral sclerosis: a case-control study and literature review. | Wei Q | Scientific reports | 2017 | PMID: 28291249 |
The G41D mutation in the superoxide dismutase 1 gene is associated with slow motor neuron progression and mild cognitive impairment in a Chinese family with amyotrophic lateral sclerosis. | Niu Q | Journal of neurology, neurosurgery, and psychiatry | 2016 | PMID: 26069299 |
A novel monoclonal antibody reveals a conformational alteration shared by amyotrophic lateral sclerosis-linked SOD1 mutants. | Fujisawa T | Annals of neurology | 2012 | PMID: 23280792 |
Mutation-dependent polymorphism of Cu,Zn-superoxide dismutase aggregates in the familial form of amyotrophic lateral sclerosis. | Furukawa Y | The Journal of biological chemistry | 2010 | PMID: 20404329 |
Variation in aggregation propensities among ALS-associated variants of SOD1: correlation to human disease. | Prudencio M | Human molecular genetics | 2009 | PMID: 19483195 |
Corticomotoneuronal dysfunction in ALS patients with different SOD1 mutations. | Stewart HG | Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology | 2006 | PMID: 16793335 |
Rapid disease progression correlates with instability of mutant SOD1 in familial ALS. | Sato T | Neurology | 2005 | PMID: 16291929 |
Epidemiology of mutations in superoxide dismutase in amyotrophic lateral sclerosis. | Cudkowicz ME | Annals of neurology | 1997 | PMID: 9029070 |
Characterization of wild-type and amyotrophic lateral sclerosis-related mutant Cu,Zn-superoxide dismutases overproduced in baculovirus-infected insect cells. | Fujii J | Journal of neurochemistry | 1995 | PMID: 7891072 |
Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. | Rosen DR | Nature | 1993 | PMID: 8446170 |
Text-mined citations for rs121912434 ...
HelpRecord last updated Feb 14, 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.