Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003537297 | SCV000963440 | uncertain significance | Familial adenomatous polyposis 1 | 2020-12-10 | criteria provided, single submitter | clinical testing | 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with APC-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with serine at codon 1388 of the APC protein (p.Thr1388Ser). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and serine. |
Ambry Genetics | RCV001021977 | SCV001183660 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-07 | criteria provided, single submitter | clinical testing | The p.T1388S variant (also known as c.4162A>T), located in coding exon 15 of the APC gene, results from an A to T substitution at nucleotide position 4162. The threonine at codon 1388 is replaced by serine, an amino acid with similar properties. This amino acid position is highly 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. |