ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3970C>G (p.Pro1324Ala) (rs587779792)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115089 SCV000148998 uncertain significance not provided 2013-10-17 criteria provided, single submitter clinical testing This variant is denoted APC c.3970C>G at the cDNA level, p.Pro1324Ala (P1324A) at the protein level, and results in the change of a Proline to an Alanine (CCA>GCA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Pro1324Ala was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a semi-conservative substitution of a neutral non-polar amino acid for a neutral non-polar one, altering a position that is well conserved throughout evolution and is located in the in a region involved in ubiquitination leading to APC downregulation. In silico analyses predict this variant to have a benign effect on protein structure and function. Based on currently available information, it is unclear whether APC Pro1324Ala is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000528782 SCV000647484 uncertain significance Familial adenomatous polyposis 1 2017-05-09 criteria provided, single submitter clinical testing This sequence change replaces proline with alanine at codon 1324 of the APC protein (p.Pro1324Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an APC-related disease. ClinVar contains an entry for this variant (Variation ID: 127292). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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