Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000306597 | SCV000349074 | uncertain significance | Hereditary pancreatitis | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| ARUP Laboratories, |
RCV000306597 | SCV001160180 | uncertain significance | Hereditary pancreatitis | 2018-12-26 | criteria provided, single submitter | clinical testing | The CTRC c.26C>T; p.Ala9Val variant (rs772818172), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 292904). This variant is only observed on two alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The alanine at codon 9 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Due to limited information, the clinical significance of the p.Ala9Val variant is uncertain at this time. |
| Mayo Clinic Laboratories, |
RCV001508847 | SCV001715258 | uncertain significance | not provided | 2019-07-29 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000306597 | SCV002244347 | uncertain significance | Hereditary pancreatitis | 2023-06-09 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 292904). 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 CTRC protein function. This variant has not been reported in the literature in individuals affected with CTRC-related conditions. This variant is present in population databases (rs772818172, gnomAD 0.002%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 9 of the CTRC protein (p.Ala9Val). |
| Ambry Genetics | RCV000306597 | SCV002742736 | uncertain significance | Hereditary pancreatitis | 2023-10-10 | criteria provided, single submitter | clinical testing | The p.A9V variant (also known as c.26C>T), located in coding exon 1 of the CTRC gene, results from a C to T substitution at nucleotide position 26. The alanine at codon 9 is replaced by valine, an amino acid with similar properties. This amino acid position is not 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. |