ClinVar Miner

Submissions for variant NM_000038.6(APC):c.8416C>G (p.Pro2806Ala) (rs587780608)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000122811 SCV000166068 uncertain significance Familial adenomatous polyposis 1 2018-08-11 criteria provided, single submitter clinical testing This sequence change replaces proline with alanine at codon 2806 of the APC protein (p.Pro2806Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. This variant is present in population databases (rs587780608, ExAC 0.002%). This variant has not been reported in the literature in individuals with a APC-related disease. ClinVar contains an entry for this variant (Variation ID: 135726). 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: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant has uncertain impact on APC function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Counsyl RCV000122811 SCV000487769 uncertain significance Familial adenomatous polyposis 1 2015-11-21 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000503195 SCV000591221 pathogenic Familial adenomatous polyposis criteria provided, single submitter clinical testing
Ambry Genetics RCV000564540 SCV000667276 uncertain significance Hereditary cancer-predisposing syndrome 2016-12-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000564540 SCV000687176 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-25 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587667 SCV000694144 uncertain significance not provided 2016-04-01 criteria provided, single submitter clinical testing Variant summary: The APC c.8416C>G variant affects a conserved nucleotide, resulting in amino acid change from Pro to Ala. 4/4 in-silico tools predict damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 1/119236 control chromosomes at a frequency of 0.0000084, which does not significantly exceed maximal expected frequency of a pathogenic APC allele (0.0000602). The variant of interest has not, to our knowledge, been reported in affected individuals via publications, nor evaluated for functional impact by in vivo/vitro studies. One clinical lab has classified the variant as a VUS. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.

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