Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002230326 | SCV000543741 | uncertain significance | Juvenile polyposis syndrome | 2016-10-26 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SMAD4-related disease. This sequence change replaces leucine with phenylalanine at codon 533 of the SMAD4 protein (p.Leu533Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. |