Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002328412 | SCV002637164 | uncertain significance | Hereditary pancreatitis | 2022-02-28 | criteria provided, single submitter | clinical testing | The p.L149F variant (also known as c.445C>T), located in coding exon 5 of the CTRC gene, results from a C to T substitution at nucleotide position 445. The leucine at codon 149 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |
Mayo Clinic Laboratories, |
RCV003481278 | SCV004227773 | uncertain significance | not provided | 2022-09-14 | criteria provided, single submitter | clinical testing | PM2 |
Labcorp Genetics |
RCV002328412 | SCV004304112 | uncertain significance | Hereditary pancreatitis | 2024-01-18 | 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 149 of the CTRC protein (p.Leu149Phe). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CTRC-related conditions. ClinVar contains an entry for this variant (Variation ID: 1740761). 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 CTRC protein function with a negative predictive value of 80%. 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. |