Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV000755996 | SCV000883690 | pathogenic | not provided | 2017-09-26 | criteria provided, single submitter | clinical testing | The CTRC c.308delG; p.Gly103fs variant (rs773119534) has been reported in a patient with hereditary chronic pancreatitis (Rosendahl 2008) and is only observed on two alleles in the Genome Aggregation Database. This variant introduces a frameshift by deleting a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered pathogenic. REFERENCES Rosendahl J et al. Chymotrypsin C (CTRC) variants that diminish activity or secretion are associated with chronic pancreatitis. Nat Genet. 2008; 40(1):78-82. |
Labcorp Genetics |
RCV000806787 | SCV000946805 | uncertain significance | Hereditary pancreatitis | 2022-05-03 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs773119534, gnomAD 0.008%). This sequence change creates a premature translational stop signal (p.Gly103Valfs*31) in the CTRC gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in CTRC cause disease. This premature translational stop signal has been observed in individual(s) with hereditary pancreatitis (PMID: 18059268, 28502372). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 618049). |
Ambry Genetics | RCV000806787 | SCV002606369 | pathogenic | Hereditary pancreatitis | 2021-09-22 | criteria provided, single submitter | clinical testing | The c.308delG pathogenic mutation, located in coding exon 4 of the CTRC gene, results from a deletion of one nucleotide at nucleotide position 308, causing a translational frameshift with a predicted alternate stop codon (p.G103Vfs*31). This variant was detected in an individual with hereditary chronic pancreatitis; it was not detected in individuals with idiopathic chronic pancreatitis or unaffected controls from the same study (Rosendahl J et al. Nat Genet, 2008 Jan;40:78-82). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |