Submissions for variant NM_007272.3(CTRC):c.-59C>T

dbSNP: rs183658182

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000230316	SCV000289728	benign	Hereditary pancreatitis	2022-01-27	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000230316	SCV001157236	uncertain significance	Hereditary pancreatitis	2023-02-23	criteria provided, single submitter	clinical testing	The CTRC c.-59C>T variant (rs183658182) has been reported in pancreatitis patients (Ballard 2015, Masson 2008), but not at a significantly higher frequency compared to unaffected individuals. This variant is found in the non-Finnish European population with an allele frequency of 0.337% (52/15,428 alleles) in the Genome Aggregation Database. This variant occurs in the 5' untranslated region at a nucleotide that is weakly conserved and does not create a novel protein translation start codon. Due to limited information, the clinical significance of this variant is uncertain at this time. References: Ballard DD et al. Evaluating Adults With Idiopathic Pancreatitis for Genetic Predisposition: Higher Prevalence of Abnormal Results With Use of Complete Gene Sequencing. Pancreas. 2015 Jan;44(1):116-21. PMID: 25251442. Masson E et al. Association of rare chymotrypsinogen C (CTRC) gene variations in patients with idiopathic chronic pancreatitis. Hum Genet. 2008 Feb;123(1):83-91. PMID: 18172691.
Ambry Genetics	RCV000230316	SCV002657542	likely benign	Hereditary pancreatitis	2018-09-24	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics	RCV000230316	SCV002790191	uncertain significance	Hereditary pancreatitis	2021-12-06	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003982975	SCV004797128	uncertain significance	CTRC-related disorder	2024-02-21	criteria provided, single submitter	clinical testing	The CTRC c.-59C>T variant is located in the 5' untranslated region. This variant was reported in four individuals with idiopathic chronic pancreatitis, one individual with familial chronic pancreatitis, and one individual with hereditary pancreatitis but was also found in two controls (Table 4, Masson et al. 2008. PubMed ID: 18172691). This variant was also reported in two individuals with unexplained pancreatitis, although one individual also carried a CFTR variant (Supplementary Table, Ballard et al. 2015. PubMed ID: 25251442). This variant is reported in 0.34% of alleles in individuals of European (Non-Finnish) descent in gnomAD, including one homozygous individual, and has conflicting interpretations regarding its pathogenicity in ClinVar, ranging from benign to uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/240761/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Breakthrough Genomics, Breakthrough Genomics	RCV004691115	SCV005186478	uncertain significance	not provided		criteria provided, single submitter	not provided