Test panel testing 2020-07-27

Gene: PRSS1

Green List (high evidence)

Testing adding a review
Sources: Literature

Created: 27 Jul 2020, 10:25 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Green List (high evidence)

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 given

Created: 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.

Green List (high evidence)

Test of Green Review

Created: 27 Jul 2020, 12:09 p.m. | Last Modified: 27 Jul 2020, 12:09 p.m.

Panel Version: 1.6

Comment when marking as ready: marking as ready

Created: 27 Jul 2020, 11:21 a.m. | Last Modified: 27 Jul 2020, 11:21 a.m.

Panel Version: 0.9

adding a comment as a curator

Created: 27 Jul 2020, 11:19 a.m. | Last Modified: 27 Jul 2020, 11:19 a.m.

Panel Version: 0.9

Comment on publications: Publications from OMIM

Created: 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 Gene2Phenotype

Created: 12 Sep 2018, 10:07 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Phenotype 3

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Green List (high evidence)