Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003444845 | SCV001562861 | uncertain significance | Familial adenomatous polyposis 1 | 2020-08-15 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with serine at codon 381 of the APC protein (p.Ala381Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is not present in population databases (ExAC no frequency). 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. 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with APC-related conditions. |
| St. |
RCV003444845 | SCV004171486 | uncertain significance | Familial adenomatous polyposis 1 | 2023-10-18 | criteria provided, single submitter | clinical testing | The APC c.1141G>T (p.Ala381Ser) missense change has a maximum subpopulation frequency of 0.0032% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in the literature in individuals with APC-related disease. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |