ClinVar Miner

Submissions for variant NM_001868.4(CPA1):c.776C>T (p.Ala259Val)

gnomAD frequency: 0.00003  dbSNP: rs1009079470
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001307869 SCV001497297 uncertain significance not provided 2023-12-14 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 259 of the CPA1 protein (p.Ala259Val). This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with CPA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1010268). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CPA1 protein function with a negative predictive value of 80%. 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.
Ambry Genetics RCV003166754 SCV003911947 uncertain significance Hereditary pancreatitis 2023-01-11 criteria provided, single submitter clinical testing The p.A259V variant (also known as c.776C>T), located in coding exon 7 of the CPA1 gene, results from a C to T substitution at nucleotide position 776. The alanine at codon 259 is replaced by valine, an amino acid with similar properties. This alteration was identified in an individual with a family history of pancreatic cancer (Abe T et al. J Clin Oncol, 2019 May;37:1070-1080). This amino acid position is well conserved in available vertebrate species. 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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