Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002366632 | SCV002659464 | uncertain significance | Hereditary pancreatitis | 2024-09-19 | criteria provided, single submitter | clinical testing | The p.L407F variant (also known as c.1219C>T), located in coding exon 10 of the CPA1 gene, results from a C to T substitution at nucleotide position 1219. The leucine at codon 407 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is well conserved in available 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. |
| Labcorp Genetics |
RCV003718531 | SCV004511580 | uncertain significance | not provided | 2023-06-22 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 407 of the CPA1 protein (p.Leu407Phe). This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with CPA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1752399). 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. 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. |