ClinVar Miner

Submissions for variant NM_007272.3(CTRC):c.217G>A (p.Ala73Thr) (rs515726209)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000119044 SCV000958881 uncertain significance Hereditary pancreatitis 2019-12-02 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 73 of the CTRC protein (p.Ala73Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs515726209, ExAC 0.5%). This variant has been reported in individuals affected with chronic pancreatitis (PMID: 18059268, 22580415, 25569187, 18172691). Case-control studies have shown that this variant is over-represented in individuals with chronic pancreatitis (PMID: 18059268, 22580415), but due to the small size of these study populations, reliable risk assessments cannot be made at this time. ClinVar contains an entry for this variant (Variation ID: 132149). Experimental studies have shown that this missense change does not affect CTRC catalytic activity, but causes impaired secretion and retainment of the protein in the endoplasmic reticulum (ER), followed by ER stress and increased apoptosis in pancreatic acinar cells (PMID: 18059268, 22942235, 26022124). In summary, this variant has been reported in patients with chronic pancreatitis and experimental studies have shown that it leads to defective protein function. However, this variant is also present at a high frequency in the unaffected South Asian population. For these reasons, this variant has been classified as a Variant of Uncertain Significance.
GeneReviews RCV000119044 SCV000153750 pathogenic Hereditary pancreatitis 2014-03-13 no assertion criteria provided literature only

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