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rs74315403

From SNPedia

Orientationplus
Stabilizedplus
Geno Mag Summary
(A;G) 4 PrP D178N pathogenic mutation - leads to CJD or FFI
(G;G) 0 PrP codon 178 (D) - non pathogenic variant


Make rs74315403(A;A)
ReferenceGRCh38 38.1/141
Chromosome20
Position4699752
GenePRNP
is asnp
is mentioned by
dbSNPrs74315403
ebirs74315403
HLIrs74315403
Exacrs74315403
Varsomers74315403
Maprs74315403
PheGenIrs74315403
hapmaprs74315403
1000 genomesrs74315403
hgdprs74315403
ensemblrs74315403
gopubmedrs74315403
geneviewrs74315403
scholarrs74315403
googlers74315403
pharmgkbrs74315403
gwascentralrs74315403
openSNPrs74315403
23andMers74315403
23andMe allrs74315403
SNP Nexus

SNPshotrs74315403
SNPdbers74315403
MSV3drs74315403
GWAS Ctlgrs74315403
Max Magnitude4
OMIM176640
Desc
Variant0007
Relatedalso
OMIM176640
Desc
Variant0010
Relatedalso
ClinVar
Risk rs74315403(A;A)
Alt rs74315403(A;A)
Reference rs74315403(G;G)
Significance Pathogenic
Disease Jakob-Creutzfeldt disease Fatal familial insomnia Genetic prion diseases
Variation info
Gene PRNP
CLNDBN Jakob-Creutzfeldt disease Fatal familial insomnia Genetic prion diseases
Reversed 0
HGVS NC_000020.10:g.4680398G>A
CLNSRC OMIM Allelic Variant
CLNACC RCV000014336.24, RCV000014337.24, RCV000020248.1, RCV000032588.27,



This SNP codes for residue 178 of the Prion protein gene. Normally Aspartate, a polymorphism can create the D178N mutation which is linked to inherited Creutzfeldt-Jakob disease or Fatal Familial Insomnia. A number of factors influence this, including PrP codon 129, Rs1799990, with 129MM homozygotes being more likely to develop Fatal Familial Insomnia.

2016 Nature essay about this mutation, discussing use of ExAC to estimate penetrance (which at least for this mutation, D178N, turns out to be high): http://www.nature.com/news/a-radical-revision-of-human-genetics-1.20779

References[edit]

[PMID 12420099] Mutations of the prion protein gene phenotypic spectrum.

[PMID 1671440] The initial discovery of the D178N mutation in a Finnish family

[PMID 1353341] Linkage analysis of 7 families indicated strong likelihood of developing Creuzfeldt-Jakob disease given the D178N mutation, with a LOD score of 5.30.

[PMID 16227536OA-icon.png] Clinical, pathological, and genetic data were determined for a number of D178N patients, showing that symptoms lay on a spectrum from typical Creutzfeldt-Jakob disease to Fatal Familial Insomnia.