Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000119216 | SCV000153958 | uncertain significance | Familial adenomatous polyposis 1 | 2018-05-22 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with alanine at codon 2680 of the APC protein (p.Pro2680Ala). 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). This variant has not been reported in the literature in individuals with APC-related disease. ClinVar contains an entry for this variant (Variation ID: 132756). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 | RCV000575859 | SCV000672522 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-12-20 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: Insufficient evidence |
| Integrated Genetics/Laboratory Corporation of America | RCV000588854 | SCV000694133 | uncertain significance | not provided | 2016-11-25 | criteria provided, single submitter | clinical testing | Variant summary: The APC c.8038C>G (p.Pro2680Ala) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant is absent in 121286 control chromosomes. In addition, one other clinical diagnostic laboratory classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available. |