Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001026797 | SCV001189248 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-06-21 | criteria provided, single submitter | clinical testing | The p.H2591L variant (also known as c.7772A>T), located in coding exon 15 of the APC gene, results from an A to T substitution at nucleotide position 7772. The histidine at codon 2591 is replaced by leucine, an amino acid with similar properties. This amino acid position is not well 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. |
Invitae | RCV003649254 | SCV001387653 | uncertain significance | Familial adenomatous polyposis 1 | 2019-04-19 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with leucine at codon 2591 of the APC protein (p.His2591Leu). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and leucine. 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 conditions. 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 and their clinical significance is uncertain. 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. |