Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003534592 | SCV000818525 | uncertain significance | Familial adenomatous polyposis 1 | 2018-03-24 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with glutamic acid at codon 1199 of the APC protein (p.Lys1199Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with APC-related disease. 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. |
Ambry Genetics | RCV002334284 | SCV002619440 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-08 | criteria provided, single submitter | clinical testing | The p.K1199E variant (also known as c.3595A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 3595. The lysine at codon 1199 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |