Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002369020 | SCV002658033 | uncertain significance | Hereditary pancreatitis | 2023-01-24 | criteria provided, single submitter | clinical testing | The p.C212Y variant (also known as c.635G>A), located in coding exon 6 of the CTRC gene, results from a G to A substitution at nucleotide position 635. The cysteine at codon 212 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV002369020 | SCV004552021 | uncertain significance | Hereditary pancreatitis | 2023-02-09 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 212 of the CTRC protein (p.Cys212Tyr). 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: 1753046). 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 expected to disrupt CTRC 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. |