Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV003625109 | SCV004562696 | likely pathogenic | Hereditary pancreatitis | 2023-10-04 | criteria provided, single submitter | clinical testing | The CTRC c.132G>A; p.Gln44= variant (rs901779500) is reported in the literature in an individual affected with chronic pancreatitis (Beer 2014, Rosendahl 2013). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This is a synonymous variant in a highly conserved nucleotide, and computational analyses (Alamut Visual Plus v.1.5.1) predict that this variant may impact splicing by weakening the nearby canonical donor splice site, and a mini-gene assay confirmed this variant results in aberrant splicing (Beer 2014). Based on available information, this variant is considered to be likely pathogenic. References: Beer S et al. Exonic variants affecting pre-mRNA splicing add to genetic burden in chronic pancreatitis. Gut. 2014 May;63(5):860-1. PMID: 24052272. Rosendahl J et al. CFTR, SPINK1, CTRC and PRSS1 variants in chronic pancreatitis: is the role of mutated CFTR overestimated? Gut. 2013 Apr;62(4):582-92. PMID: 22427236. |
| Ambry Genetics | RCV003625109 | SCV005025653 | uncertain significance | Hereditary pancreatitis | 2024-02-12 | criteria provided, single submitter | clinical testing | The c.132G>A variant (also known as p.Q44Q), located in coding exon 2 of the CTRC gene, results from a G to A substitution at nucleotide position 132. This nucleotide substitution does not change the glutamine at codon 44. However, this change occurs in the last base pair of coding exon 2, which makes it likely to have some effect on normal mRNA splicing. This variant was identified in one individual under 20 years of age with chronic pancreatitis (Rosendahl J et al. Gut, 2013 Apr;62:582-92). This variant demonstrated reduced levels of the correctly spliced mRNA and the accumulation of the unspliced species in a minigene analysis in HEK293T cells (Beer S et al. Gut, 2014 May;63:860-1). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. |