ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3946G>C (p.Ala1316Pro)

gnomAD frequency: 0.00002  dbSNP: rs761621587
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001021490 SCV001183115 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-15 criteria provided, single submitter clinical testing The p.A1316P variant (also known as c.3946G>C), located in coding exon 15 of the APC gene, results from a G to C substitution at nucleotide position 3946. The alanine at codon 1316 is replaced by proline, an amino acid with highly similar properties. This amino acid position is poorly 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.
Color Diagnostics, LLC DBA Color Health RCV001021490 SCV001345154 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces alanine with proline at codon 1316 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has been identified in 5/251164 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae RCV003769545 SCV002287361 uncertain significance Familial adenomatous polyposis 1 2022-11-04 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 APC protein function. ClinVar contains an entry for this variant (Variation ID: 824410). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (rs761621587, gnomAD 0.02%). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1316 of the APC protein (p.Ala1316Pro).

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