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NM_000454.5(SOD1):c.10A>G (p.Lys4Glu) AND Amyotrophic lateral sclerosis type 1

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 12, 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:
RCV003064620.2

Allele description

NM_000454.5(SOD1):c.10A>G (p.Lys4Glu)

Genes:
SOD1-DT:SOD1 divergent transcript [Gene - HGNC]
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.10A>G (p.Lys4Glu)
HGVS:
  • NC_000021.9:g.31659779A>G
  • NG_008689.1:g.5158A>G
  • NM_000454.5:c.10A>GMANE SELECT
  • NP_000445.1:p.Lys4Glu
  • NP_000445.1:p.Lys4Glu
  • LRG_652t1:c.10A>G
  • LRG_652:g.5158A>G
  • LRG_652p1:p.Lys4Glu
  • NC_000021.8:g.33032092A>G
  • NM_000454.4:c.10A>G
Protein change:
K4E
Molecular consequence:
  • NM_000454.5:c.10A>G - 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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003443854Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Aug 12, 2022) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Development of a high-throughput microarray-based resequencing system for neurological disorders and its application to molecular genetics of amyotrophic lateral sclerosis.

Takahashi Y, Seki N, Ishiura H, Mitsui J, Matsukawa T, Kishino A, Onodera O, Aoki M, Shimozawa N, Murayama S, Itoyama Y, Suzuki Y, Sobue G, Nishizawa M, Goto J, Tsuji S.

Arch Neurol. 2008 Oct;65(10):1326-32. doi: 10.1001/archneur.65.10.1326.

PubMed [citation]
PMID:
18852346

Recurrent K3E mutation in Cu/Zn superoxide dismutase gene associated with amyotrophic lateral sclerosis.

Kuźma-Kozakiewicz M, Berdyński M, Morita M, Takahashi Y, Kawata A, Kaida K, Kaźmierczak B, Lusakowska A, Goto J, Tsuji S, Zekanowski C, Kwieciński H.

Amyotroph Lateral Scler Frontotemporal Degener. 2013 Dec;14(7-8):608-14. doi: 10.3109/21678421.2013.812119. Epub 2013 Jul 30.

PubMed [citation]
PMID:
23898858
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV003443854.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

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 K3E. This missense change has been observed in individuals with amyotrophic lateral sclerosis (PMID: 18852346, 23898858, 32729725). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 4 of the SOD1 protein (p.Lys4Glu). Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on SOD1 function (PMID: 23280792). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 16, 2024