Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000704070 | SCV000833004 | uncertain significance | Hereditary pancreatitis | 2024-12-29 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 12 of the PRSS1 protein (p.Ala12Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with PRSS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 580510). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PRSS1 protein function. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001192436 | SCV001360553 | uncertain significance | not specified | 2019-01-15 | criteria provided, single submitter | clinical testing | Variant summary: PRSS1 c.35C>T (p.Ala12Val) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.1e-06 in 246030 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.35C>T in individuals affected with Chronic Pancreatitis Risk and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV000704070 | SCV002614939 | uncertain significance | Hereditary pancreatitis | 2023-03-11 | criteria provided, single submitter | clinical testing | The p.A12V variant (also known as c.35C>T), located in coding exon 1 of the PRSS1 gene, results from a C to T substitution at nucleotide position 35. The alanine at codon 12 is replaced by valine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| ARUP Laboratories, |
RCV000704070 | SCV005876023 | uncertain significance | Hereditary pancreatitis | 2024-09-26 | criteria provided, single submitter | clinical testing | The PRSS1 c.35C>T; p.Ala12Val variant (rs772363999), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 580510). This variant is only observed on two alleles in the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.491). Due to limited information, the clinical significance of this variant is uncertain at this time. |