ClinVar Miner

Submissions for variant NM_007272.3(CTRC):c.674A>C (p.Glu225Ala) (rs201486613)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001000068 SCV000289733 benign Hereditary pancreatitis 2019-12-31 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001000068 SCV000883691 uncertain significance Hereditary pancreatitis 2019-02-19 criteria provided, single submitter clinical testing The CTRC c.674A>C; p.Glu225Ala variant (rs201486613) is described in the medical literature in individuals with pancreatitis (Beer 2013, Koziel 2015), but also described in individuals without any disease (Koziel 2015, Rosendahl 2008, Zhou 2011). This variant is reported in ClinVar (Variation ID: 240766). It is found in the general population with an overall allele frequency of 0.04% (115/282830 alleles, including 1 homozygote) in the Genome Aggregation Database. The glutamic acid at codon 225 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Additionally, experiments in cell culture show this variant does not affect protein stability or activity (Beer 2013). Considering available information, there is insufficient evidence to classify this variant with certainty. REFERENCES Beer S et al. Comprehensive functional analysis of chymotrypsin C (CTRC) variants reveals distinct loss-of-function mechanisms associated with pancreatitis risk. Gut. 2013 Nov;62(11):1616-24. Koziel D et al. Genetic mutations in SPINK1, CFTR, CTRC genes in acute pancreatitis. BMC Gastroenterol. 2015 Jun 23;15:70. Rosendahl J et al. Chymotrypsin C (CTRC) variants that diminish activity or secretion are associated with chronic pancreatitis. Nat Genet. 2008 Jan;40(1):78-82. Zhou J et al. Chymotrypsin C mutations in chronic pancreatitis. J Gastroenterol Hepatol. 2011 Aug;26(8):1238-46.
Ambry Genetics RCV001025606 SCV001187831 uncertain significance Inborn genetic diseases 2019-06-18 criteria provided, single submitter clinical testing Insufficient evidence
Illumina Clinical Services Laboratory,Illumina RCV001000068 SCV001256380 uncertain significance Hereditary pancreatitis 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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