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NM_000454.5(SOD1):c.376G>C (p.Asp126His) AND Amyotrophic lateral sclerosis type 1

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 11, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV003064623.3

Allele description [Variation Report for NM_000454.5(SOD1):c.376G>C (p.Asp126His)]

NM_000454.5(SOD1):c.376G>C (p.Asp126His)

Gene:
SOD1:superoxide dismutase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
21q22.11
Genomic location:
Preferred name:
NM_000454.5(SOD1):c.376G>C (p.Asp126His)
HGVS:
  • NC_000021.9:g.31668489G>C
  • NG_008689.1:g.13868G>C
  • NM_000454.5:c.376G>CMANE SELECT
  • NP_000445.1:p.Asp126His
  • NP_000445.1:p.Asp126His
  • LRG_652t1:c.376G>C
  • LRG_652:g.13868G>C
  • LRG_652p1:p.Asp126His
  • NC_000021.8:g.33040802G>C
  • NM_000454.4:c.376G>C
Protein change:
D126H
Molecular consequence:
  • NM_000454.5:c.376G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Amyotrophic lateral sclerosis type 1 (ALS1)
Synonyms:
AMYOTROPHIC LATERAL SCLEROSIS 1, FAMILIAL
Identifiers:
MONDO: MONDO:0007103; MedGen: C1862939; Orphanet: 803; OMIM: 105400

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV003443856Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Jul 11, 2022)
germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Familial ALS-superoxide dismutases associate with mitochondria and shift their redox potentials.

Ferri A, Cozzolino M, Crosio C, Nencini M, Casciati A, Gralla EB, Rotilio G, Valentine JS, Carrì MT.

Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13860-5. Epub 2006 Aug 30.

PubMed [citation]
PMID:
16945901
PMCID:
PMC1557633

Variation in aggregation propensities among ALS-associated variants of SOD1: correlation to human disease.

Prudencio M, Hart PJ, Borchelt DR, Andersen PM.

Hum Mol Genet. 2009 Sep 1;18(17):3217-26. doi: 10.1093/hmg/ddp260. Epub 2009 May 30.

PubMed [citation]
PMID:
19483195
PMCID:
PMC2722984
See all PubMed Citations (9)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003443856.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

Experimental studies have shown that this missense change affects SOD1 function (PMID: 16945901, 19483195, 19635794, 20399791, 23280792, 25600987, 26084641). 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. 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. This variant is also known as p.Asp125His. This missense change has been observed in individual(s) with clinical features of amyotrophic lateral sclerosis (PMID: 8528216). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 126 of the SOD1 protein (p.Asp126His).

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

Last Updated: Sep 29, 2024