ClinVar Miner

Submissions for variant NM_001379610.1(SPINK1):c.206C>T (p.Thr69Ile)

gnomAD frequency: 0.00001  dbSNP: rs576564400
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000506639 SCV000605253 uncertain significance not specified 2017-03-27 criteria provided, single submitter clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000660289 SCV000782317 pathogenic Hereditary pancreatitis 2016-11-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000660289 SCV000951976 uncertain significance Hereditary pancreatitis 2021-02-04 criteria provided, single submitter clinical testing This variant is present in population databases (rs576564400, ExAC 0.02%). This sequence change replaces threonine with isoleucine at codon 69 of the SPINK1 protein (p.Thr69Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. 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. Experimental studies have shown that this missense change abolishes SPINK1 protein expression in an overexpression system (PMID: 22343981). This variant has been observed in an individual affected with alcoholic pancreatitis (PMID: 18182741) and in individuals with idiopathic chronic pancreatitis (PMID: 30420730). ClinVar contains an entry for this variant (Variation ID: 440299).
Ambry Genetics RCV000660289 SCV002727685 uncertain significance Hereditary pancreatitis 2021-03-10 criteria provided, single submitter clinical testing The p.T69I variant (also known as c.206C>T), located in coding exon 4 of the SPINK1 gene, results from a C to T substitution at nucleotide position 206. The threonine at codon 69 is replaced by isoleucine, an amino acid with similar properties. This alteration was identified in multiple individuals with chronic pancreatitis (Rerknimitr R et al. JOP, 2008;9:33-6; Zou WB et al. Clin Transl Gastroenterol, 2018 11;9:204). This amino acid position is poorly conserved on limited sequence alignment. 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.

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