|(A;A)||0||common in clinvar|
|(A;C)||8||Early-onset Alzheimer's disease (in some cases)|
rs63750231 consists of at least two known mutations, and so this SNP is also known as both c.839A>C, p.Glu280Ala and E280A, as well as c.839A>G, p.Glu280Gly and E280G. Both are very rare mutations in the PSEN1 gene on chromosome 14.
The rs63750231(C) allele is reported to be a dominant mutation leading to early-onset Alzheimer's disease. This was originally reported in 1995 ([PMID 7550356]), with subsequent reports based on Colombian populations, where the mutation is somewhat more frequent than in other populations. Additional information can be found in OMIM 104311.0009.
This SNP is referred to as i5047571 by 23andMe, and it is reported to assay the A/G form of this SNP (and not the A/C).
Washington Post article on the history, traces the presence of this to a 17th century conquistador.
|Disease||Alzheimer disease Alzheimer disease not provided|
|CLNDBN||Alzheimer disease, type 3 Alzheimer disease, familial, with spastic paraparesis and unusual plaques not provided|
|CLNSRC||OMIM Allelic Variant UniProtKB (protein)|
|CLNACC||RCV000019759.28, RCV000019760.26, RCV000019761.27, RCV000084381.1,|
[PMID 7550356] The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families. Alzheimer's Disease Collaborative Group.
[PMID 8837617] The E280A presenilin 1 Alzheimer mutation produces increased A beta 42 deposition and severe cerebellar pathology.
[PMID 9052708] Clinical features of early-onset Alzheimer disease in a large kindred with an E280A presenilin-1 mutation.
[PMID 11402113] Presenilin-1-associated abnormalities in regional cerebral perfusion.
[PMID 12891668] Apolipoprotein Eepsilon4 modifies Alzheimer's disease onset in an E280A PS1 kindred.