Pancreatitis
Gene: PRSS1
Comment when marking as ready: As discussed in the GMS Gastrohepatology Specialist Test Group webex call 14th Jan 2019: The Specialist Test Group agreed that there is enough evidence to rate this gene green.Created: 24 Jan 2019, 4:19 p.m.
Initial gene list and info collated by Miranda Durkie Sheffield Diagnostic Genetics Service December 2018 on behalf of the GMS Gastrohepatology specialist test group. Gene Symbol submitted: PRSS1; Suggested intial gene rating: Green; Evidence for inclusion: none given; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none givenCreated: 7 Jan 2019, 4:15 p.m.
Comment on mode of pathogenicity: Seems to be a gain-of-function mechanism.Created: 10 Dec 2018, 12:56 p.m.
This gene is within the Pancreatitis, Hereditary panel on UKGTN.Created: 6 Dec 2018, 2:09 p.m.
Comment on publications: Publications from OMIMCreated: 12 Sep 2018, 10:10 p.m.
Comment on list classification: More than 3 unrelated cases of plausible disease causing variants associated with the disorder.Created: 12 Sep 2018, 10:08 p.m.
In OMIM PRSS1 is associated with Pancreatitis, hereditary.
Numerous (> 3) cases have been reported of variants in PRSS1 being associated with the disorder, following an autosomal dominant pattern of inheritance (PMIDs: 8841182, 10204851, 10529393, 11097832, 11702203). The two most common amino acid changes associated with pancreatitis R122H and N29I significantly enhance autoactivation of human cationic trypsinogen in vitro, in a manner that correlates with the severity of clinical symptoms in hereditary pancreatitis and are therefore gain-of-function mutations
Gene conversion events with other trypsinogen genes (PMID: 15776435, 16791840), hybrid genes (PMID: 18461367) and duplication of PRSS1 have also be reported (Le Marechal et al. (2006) (PMID: 17072318). However ClinGen states there is no evidence for Triplosensitivity https://www.ncbi.nlm.nih.gov/projects/dbvar/clingen/clingen_gene.cgi?sym=prss1&subject
No information from Gene2PhenotypeCreated: 12 Sep 2018, 10:07 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Gene: prss1 has been classified as Green List (High Evidence).
Source NHS GMS was added to PRSS1. Rating Changed from Green List (high evidence) to Green List (high evidence)
Eleanor Williams: In OMIM PRSS1 is associated wi
Mode of pathogenicity for gene: PRSS1 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Tag cnv tag was added to gene: PRSS1.
Phenotypes for gene: PRSS1 were changed from to Pancreatitis, hereditary 167800
Publications for gene: PRSS1 were set to
Mode of inheritance for gene: PRSS1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Gene: prss1 has been classified as Green List (High Evidence).
PRSS1 was added to Pancreatitis panel. Sources: EUROPAC
PRSS1 was created by Ellen McDonagh