Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000222801 | SCV000276357 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-06-05 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: Insufficient or conflicting evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes) |
| Invitae | RCV000534439 | SCV000647562 | uncertain significance | Familial adenomatous polyposis 1 | 2017-04-16 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with glycine at codon 1731 of the APC protein (p.Ala1731Gly). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and glycine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an APC-related disease. ClinVar contains an entry for this variant (Variation ID: 232267). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. |