Submissions for variant NM_002769.5(PRSS1):c.386C>T (p.Pro129Leu)

dbSNP: rs768673799

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001368896	SCV001565315	uncertain significance	Hereditary pancreatitis	2020-01-31	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PRSS1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 129 of the PRSS1 protein (p.Pro129Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine.
Ambry Genetics	RCV001368896	SCV002624797	uncertain significance	Hereditary pancreatitis	2022-02-04	criteria provided, single submitter	clinical testing	The p.P129L variant (also known as c.386C>T), located in coding exon 3 of the PRSS1 gene, results from a C to T substitution at nucleotide position 386. The proline at codon 129 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002469381	SCV002766205	uncertain significance	not specified	2022-11-29	criteria provided, single submitter	clinical testing	Variant summary: PRSS1 c.386C>T (p.Pro129Leu) results in a non-conservative amino acid change located in the Serine proteases, trypsin domain (IPR001254) of the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250650 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.386C>T in individuals affected with Chronic Pancreatitis Risk and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.