Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001323692 | SCV001514618 | uncertain significance | Juvenile polyposis syndrome | 2015-09-13 | criteria provided, single submitter | clinical testing | This variant is not present in population databases and has not been reported in the literature. In summary, this is a novel missense change that is not predicted to affect protein function or cause disease. However the evidence is insufficient at this time to prove that conclusively. 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. This sequence change replaces valine with leucine at codon 475 of the SMAD4 protein (p.Val475Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. |