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NM_000021.4(PSEN1):c.1307C>A (p.Pro436Gln) AND Alzheimer disease 3

Clinical significance:Pathogenic (Last evaluated: Jun 15, 2004)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000021.4(PSEN1):c.1307C>A (p.Pro436Gln)]

NM_000021.4(PSEN1):c.1307C>A (p.Pro436Gln)

PSEN1:presenilin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000021.4(PSEN1):c.1307C>A (p.Pro436Gln)
  • NC_000014.9:g.73219192C>A
  • NG_007386.2:g.87722C>A
  • NM_000021.4:c.1307C>AMANE SELECT
  • NM_007318.3:c.1295C>A
  • NP_000012.1:p.Pro436Gln
  • NP_015557.2:p.Pro432Gln
  • LRG_224t1:c.1307C>A
  • LRG_224:g.87722C>A
  • LRG_224p1:p.Pro436Gln
  • NC_000014.8:g.73685900C>A
  • P49768:p.Pro436Gln
Protein change:
P432Q; PRO436GLN
UniProtKB: P49768#VAR_006460; OMIM: 104311.0028; dbSNP: rs121917808
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000021.4:c.1307C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007318.3:c.1295C>A - missense variant - [Sequence Ontology: SO:0001583]


Alzheimer disease 3
Alzheimer disease early onset type 3; ALZHEIMER DISEASE, FAMILIAL, 3
MONDO: MONDO:0011913; MedGen: C1843013; Orphanet: 1020; OMIM: 607822

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000040078OMIMno assertion criteria providedPathogenic
(Jun 15, 2004)
unknownliterature only

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownnot providednot providednot providednot providednot providednot providedliterature only



Somatic and germline mosaicism in sporadic early-onset Alzheimer's disease.

Beck JA, Poulter M, Campbell TA, Uphill JB, Adamson G, Geddes JF, Revesz T, Davis MB, Wood NW, Collinge J, Tabrizi SJ.

Hum Mol Genet. 2004 Jun 15;13(12):1219-24. Epub 2004 Apr 28.

PubMed [citation]

Two novel presenilin-1 mutations (Ser169Leu and Pro436Gln) associated with very early onset Alzheimer's disease.

Taddei K, Kwok JB, Kril JJ, Halliday GM, Creasey H, Hallupp M, Fisher C, Brooks WS, Chung C, Andrews C, Masters CL, Schofield PR, Martins RN.

Neuroreport. 1998 Oct 5;9(14):3335-9.

PubMed [citation]

Details of each submission

From OMIM, SCV000040078.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)


Beck et al. (2004) reported a patient with sporadic early-onset Alzheimer disease (AD3; 607822) who was a somatic mosaic for a 71111C-A transversion in exon 12 of the PSEN1 gene. The mutation, which had been described by Taddei et al. (1998), was predicted to result in substitution of glutamine at proline-436 (P436Q). The index patient presented at age 52 years with a 10-year history of progressive parkinsonian syndrome, spastic paraparesis, and dementia; she died 6 years later. The degree of mosaicism was 8% in peripheral lymphocytes and 14% in the cerebral cortex of the index patient. Her daughter, who presented at age 27 years with progressive cerebellar syndrome, spastic paraparesis, and dementia, was heterozygous for the mutation; she died 12 years after diagnosis. The authors hypothesized that mosaicism may be an important mechanism in the etiology of sporadic AD and other apparently sporadic neurodegenerative diseases such as Parkinson disease (see 168601), motor neuron disease, and Creutzfeldt-Jakob disease (123400).

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownnot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 23, 2022