NM_000454.5(SOD1):c.263T>C (p.Val88Ala) AND Amyotrophic lateral sclerosis type 1

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 30, 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:: RCV001064307.7

Allele description

NM_000454.5(SOD1):c.263T>C (p.Val88Ala)

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.263T>C (p.Val88Ala)

HGVS:

NC_000021.9:g.31667281T>C
NG_008689.1:g.12660T>C
NM_000454.5:c.263T>CMANE SELECT
NP_000445.1:p.Val88Ala
LRG_652t1:c.263T>C
LRG_652:g.12660T>C
NC_000021.8:g.33039594T>C
NM_000454.4:c.263T>C

Protein change:

V88A

Links:

dbSNP: rs1339283341

NCBI 1000 Genomes Browser:

rs1339283341

Molecular consequence:

NM_000454.5:c.263T>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001229199	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jun 30, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23280792, 14506936, 27604643, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001229199

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jun 30, 2022)

germline

clinical testing

PubMed (4)
[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

A novel monoclonal antibody reveals a conformational alteration shared by amyotrophic lateral sclerosis-linked SOD1 mutants.

Fujisawa T, Homma K, Yamaguchi N, Kadowaki H, Tsuburaya N, Naguro I, Matsuzawa A, Takeda K, Takahashi Y, Goto J, Tsuji S, Nishitoh H, Ichijo H.

Ann Neurol. 2012 Nov;72(5):739-49. doi: 10.1002/ana.23668.

PubMed [citation]

PMID:: 23280792

Sixteen novel mutations in the Cu/Zn superoxide dismutase gene in amyotrophic lateral sclerosis: a decade of discoveries, defects and disputes.

Andersen PM, Sims KB, Xin WW, Kiely R, O'Neill G, Ravits J, Pioro E, Harati Y, Brower RD, Levine JS, Heinicke HU, Seltzer W, Boss M, Brown RH Jr.

Amyotroph Lateral Scler Other Motor Neuron Disord. 2003 Jun;4(2):62-73.

PubMed [citation]

PMID:: 14506936

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001229199.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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: 858432). This variant is also known as p.Val87Ala. This missense change has been observed in individuals with clinical features of amyotrophic lateral sclerosis (PMID: 14506936, 27604643; Invitae). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 88 of the SOD1 protein (p.Val88Ala).

#	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: Mar 16, 2024

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