Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001893361 | SCV002167236 | uncertain significance | not provided | 2023-02-14 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1391981). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CPA1 protein function. This variant has not been reported in the literature in individuals affected with CPA1-related conditions. This variant is present in population databases (rs782420276, gnomAD 0.005%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 398 of the CPA1 protein (p.Pro398Ser). |
| Ambry Genetics | RCV002334823 | SCV002641902 | uncertain significance | Hereditary pancreatitis | 2024-10-27 | criteria provided, single submitter | clinical testing | The p.P398S variant (also known as c.1192C>T), located in coding exon 10 of the CPA1 gene, results from a C to T substitution at nucleotide position 1192. The proline at codon 398 is replaced by serine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, serine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |