Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000216852 | SCV000274821 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-29 | criteria provided, single submitter | clinical testing | The p.V1822G variant (also known as c.5465T>G), located in coding exon 15 of the APC gene, results from a T to G substitution at nucleotide position 5465. The valine at codon 1822 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is well 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. |
Invitae | RCV002229236 | SCV000552445 | uncertain significance | Familial adenomatous polyposis 1 | 2021-10-23 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 1822 of the APC protein (p.Val1822Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 231079). 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000589084 | SCV000694079 | uncertain significance | not specified | 2019-11-11 | criteria provided, single submitter | clinical testing | Variant summary: APC c.5465T>G (p.Val1822Gly) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 250474 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.5465T>G in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Color Diagnostics, |
RCV000216852 | SCV002053504 | likely benign | Hereditary cancer-predisposing syndrome | 2017-04-04 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000216852 | SCV002535663 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-15 | criteria provided, single submitter | curation |