Submissions for variant NM_001868.4(CPA1):c.661A>G (p.Thr221Ala)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002364604	SCV002664479	uncertain significance	Hereditary pancreatitis	2022-10-12	criteria provided, single submitter	clinical testing	The p.T221A variant (also known as c.661A>G), located in coding exon 6 of the CPA1 gene, results from an A to G substitution at nucleotide position 661. The threonine at codon 221 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003098307	SCV003021880	uncertain significance	not provided	2023-02-11	criteria provided, single submitter	clinical testing	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. 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. ClinVar contains an entry for this variant (Variation ID: 1754501). This variant has not been reported in the literature in individuals affected with CPA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 221 of the CPA1 protein (p.Thr221Ala).