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:: RCV003064620.3

Allele description [Variation Report for NM_000454.5(SOD1):c.10A>G (p.Lys4Glu)]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003443854	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 12, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 18852346, 23898858, 32729725, 23280792, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003443854

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 12, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003443854.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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