Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000522708 | SCV000617855 | uncertain significance | not provided | 2023-06-08 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23955596, 24522117) |
| Labcorp Genetics |
RCV000522708 | SCV001485723 | uncertain significance | not provided | 2025-01-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 283 of the CPA1 protein (p.Glu283Lys). This variant is present in population databases (rs782561684, gnomAD 0.0009%). This missense change has been observed in individual(s) with non-alcoholic chronic pancreatitis (PMID: 23955596). ClinVar contains an entry for this variant (Variation ID: 449568). 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) indicates that this missense variant is expected to disrupt CPA1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects CPA1 function (PMID: 23955596). 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. |
| Ambry Genetics | RCV002448571 | SCV002677616 | uncertain significance | Hereditary pancreatitis | 2022-08-01 | criteria provided, single submitter | clinical testing | The p.E283K variant (also known as c.847G>A), located in coding exon 8 of the CPA1 gene, results from a G to A substitution at nucleotide position 847. The glutamic acid at codon 283 is replaced by lysine, an amino acid with similar properties. This alteration has been detected in two individuals with non alcoholic pancreatitis (Witt H et al. Nat. Genet., 2013 Oct;45:1216-20). This amino acid position is highly 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. |
| Institute of Human Genetics, |
RCV002448571 | SCV005627536 | uncertain significance | Hereditary pancreatitis | 2024-12-17 | criteria provided, single submitter | clinical testing | Criteria applied: PS4_SUP,PM1_SUP,PP3 |