Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001002201 | SCV001160075 | uncertain significance | not specified | 2018-11-03 | criteria provided, single submitter | clinical testing | The PRSS1 c.200C>T; p.Ser67Phe (rs765342413), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is found on only four chromosomes in the Genome Aggregation Database, indicating it is not a common polymorphism. The serine at codon 67 is highly conserved, but computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Ser67Phe variant is uncertain at this time. |
| Labcorp Genetics |
RCV001860511 | SCV002210184 | uncertain significance | Hereditary pancreatitis | 2023-12-20 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 67 of the PRSS1 protein (p.Ser67Phe). 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: 811811). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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, |
RCV001002201 | SCV002571788 | uncertain significance | not specified | 2022-08-05 | criteria provided, single submitter | clinical testing | Variant summary: PRSS1 c.200C>T (p.Ser67Phe) 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 damaging effect of the variant on protein function. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.6e-05 in 251096 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.200C>T has been reported in the literature in at-least one individual reported with breast cancer (example: Huang_2018). This report does not provide unequivocal conclusions about association of the variant with Chronic Pancreatitis Risk. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have 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. |
| Ambry Genetics | RCV001860511 | SCV002719569 | uncertain significance | Hereditary pancreatitis | 2022-10-27 | criteria provided, single submitter | clinical testing | The p.S67F variant (also known as c.200C>T), located in coding exon 2 of the PRSS1 gene, results from a C to T substitution at nucleotide position 200. The serine at codon 67 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is not 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. |