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rs111033566

From SNPedia

Orientationplus
Stabilizedplus
Geno Mag Summary
(A;A) 0 common in clinvar
(A;C) 2 Problematic; maybe pathogenic for hereditary pancreatitis, maybe not
(A;T) 2 Problematic; maybe pathogenic for hereditary pancreatitis, maybe not
(T;T) 2 Problematic; maybe pathogenic for hereditary pancreatitis, maybe not
ReferenceGRCh38 38.1/141
Chromosome7
Position142750600
GenePRSS1
is asnp
is mentioned by
dbSNPrs111033566
ebirs111033566
HLIrs111033566
Exacrs111033566
Varsomers111033566
Maprs111033566
PheGenIrs111033566
hapmaprs111033566
1000 genomesrs111033566
hgdprs111033566
ensemblrs111033566
gopubmedrs111033566
geneviewrs111033566
scholarrs111033566
googlers111033566
pharmgkbrs111033566
gwascentralrs111033566
openSNPrs111033566
23andMers111033566
23andMe allrs111033566
SNP Nexus

SNPshotrs111033566
SNPdbers111033566
MSV3drs111033566
GWAS Ctlgrs111033566
Max Magnitude2

aka c.86A>T, p.Asn29Ile and N29I, but also, c.86A>C, p.Asn29Thr and N29T

There is a major disconnect between the literature on hereditary pancreatitis about the mutations at this SNP compared to the frequencies observed for these mutations in populations (i.e. populations that are mostly healthy and where the incidence of pancreatitis is quite low).

Specifically, numerous publications, ClinVar, and the Pancreas Genetics database all state that both the N29I and N29T mutations are dominant and pathogenic (for hereditary pancreatitis).

However, allele frequencies for the rs111033566(T) allele are around 47%, a frequency so high it's extremely unlikely that the allele represents a pathogenic mutation for a rare condition, even one with variable penetrance.

It is unclear what the basis for this discrepancy is; anyone with evidence or an explanation should post to this SNP's Discussion page.

OMIM276000
Desc
Variant0002
Relatedalso
ClinVar
Risk rs111033566(C,T;C,T)
Alt rs111033566(C,T;C,T)
Reference rs111033566(A;A)
Significance Pathogenic
Disease Hereditary pancreatitis
Variation info
Gene PRSS1
CLNDBN Hereditary pancreatitis
Reversed 0
HGVS NC_000007.13:g.142458451A>C; NC_000007.13:g.142458451A>T
CLNSRC OMIM Allelic Variant
CLNACC RCV000031923.1, RCV000012652.20,


[PMID 185115] [Participation of the beta-receptor system in the genesis of the carotid aortic baroreceptor reflex in the dog (author's transl)].


[PMID 9633818] Mutations of the cationic trypsinogen in hereditary pancreatitis.


[PMID 11719509] Hereditary pancreatitis caused by a novel PRSS1 mutation (Arg-122 --> Cys) that alters autoactivation and autodegradation of cationic trypsinogen.


[PMID 11788572OA-icon.png] Novel cationic trypsinogen (PRSS1) N29T and R122C mutations cause autosomal dominant hereditary pancreatitis.


[PMID 11842279] R116C mutation of cationic trypsinogen in a Turkish family with recurrent pancreatitis illustrates genetic microheterogeneity of hereditary pancreatitis.


[PMID 12011155OA-icon.png] Mutations in the pancreatic secretory trypsin inhibitor gene (PSTI/SPINK1) rather than the cationic trypsinogen gene (PRSS1) are significantly associated with tropical calcific pancreatitis.