Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000031923 | SCV001137526 | pathogenic | Hereditary pancreatitis | 2023-03-30 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000031923 | SCV001482225 | pathogenic | Hereditary pancreatitis | 2023-04-27 | criteria provided, single submitter | clinical testing | Variant summary: PRSS1 c.86A>C (p.Asn29Thr) results in a non-conservative amino acid change located in the Serine proteases, trypsin domain (IPR001254) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 155926 control chromosomes (gnomAD). c.86A>C has been reported in the literature in multiple individuals affected with Chronic Pancreatitis and co-segregated with the disease (Pfutzer_2002, Szmola_2010, Dytz_2015, Xiao_2017). Additionally, in one family, 8 out of 10 individuals carrying this variant developed pancreatitis and penetrance of this variant in this family was 80%, which is the same penetrance rate as the most frequently described R122H and N29I mutations (Dytz_2015). These data indicate that the variant is very likely to be associated with disease. Functional studies report this variant results in a gain-of-function that leads to an increased rate of autoactivation and increased trypsin stability (Sahin-Toth_2000, Szabo_2012). In addition, another missense at the same codon, N29I, has been classified as pathogenic in our lab, suggesting that it is a clinically significant residue. One ClinVar submitter (evaluation after 2014) cites this variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |