NM_000021.4(PSEN1):c.424G>A (p.Val142Ile) AND Alzheimer disease

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 1, 2017
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:: RCV000736266.1

Allele description [Variation Report for NM_000021.4(PSEN1):c.424G>A (p.Val142Ile)]

NM_000021.4(PSEN1):c.424G>A (p.Val142Ile)

Gene:

PSEN1:presenilin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q24.2

Genomic location:

Preferred name:

NM_000021.4(PSEN1):c.424G>A (p.Val142Ile)

HGVS:

NC_000014.9:g.73173651G>A
NG_007386.2:g.42181G>A
NM_000021.4:c.424G>AMANE SELECT
NM_007318.3:c.412G>A
NP_000012.1:p.Val142Ile
NP_015557.2:p.Val138Ile
LRG_224t1:c.424G>A
LRG_224:g.42181G>A
LRG_224p1:p.Val142Ile
NC_000014.8:g.73640359G>A
NM_000021.3:c.424G>A

Protein change:

V138I

Links:

dbSNP: rs1566630910

NCBI 1000 Genomes Browser:

rs1566630910

Molecular consequence:

NM_000021.4:c.424G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_007318.3:c.412G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Alzheimer disease
Synonyms:: Presenile and senile dementia; Alzheimer's disease
Identifiers:: MONDO: MONDO:0004975; MeSH: D000544; MedGen: C0002395; Orphanet: 1020; Human Phenotype Ontology: HP:0002511

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000864563	Human Genetics Group at Institute of Prion Diseases London, University College London	criteria provided, single submitter (Koriath et al. 2018)	Pathogenic (Feb 1, 2017)	inherited	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000864563

Human Genetics Group at Institute of Prion Diseases London, University College London

criteria provided, single submitter

(Koriath et al. 2018)

Pathogenic
(Feb 1, 2017)

inherited

clinical testing

PubMed (1)
[See all records that cite this PMID]

Description

Confirmed by Sanger sequencing: SCV000864563

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	inherited	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Predictors for a dementia gene mutation based on gene-panel next-generation sequencing of a large dementia referral series.

Koriath C, Kenny J, Adamson G, Druyeh R, Taylor W, Beck J, Quinn L, Mok TH, Dimitriadis A, Norsworthy P, Bass N, Carter J, Walker Z, Kipps C, Coulthard E, Polke JM, Bernal-Quiros M, Denning N, Thomas R, Raybould R, Williams J, Mummery CJ, et al.

Mol Psychiatry. 2020 Dec;25(12):3399-3412. doi: 10.1038/s41380-018-0224-0. Epub 2018 Oct 2.

PubMed [citation]

PMID:: 30279455
PMCID:: PMC6330090

Details of each submission

From Human Genetics Group at Institute of Prion Diseases London, University College London, SCV000864563.1

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

Description

This result is consistent with a diagnosis of Alzheimer's disease in this patient. The PSEN1 c.424G>A p. (Val142Ile) variant has not been previously reported in the literature or to public databases of genetic variation (ExAC, EVS, 1000G), though it is likely to be pathogenic. It causes a missense change at a highly conserved amino acid located within the second transmembrane domain of the protein, a region in which several pathogenic missense mutations have been previously reported. Analysis of affected family members would assist in the interpretation of this result.

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

Last Updated: Apr 20, 2024

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