Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001010044 | SCV001170187 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-01-11 | criteria provided, single submitter | clinical testing | The p.L387V variant (also known as c.1159C>G), located in coding exon 9 of the APC gene, results from a C to G substitution at nucleotide position 1159. The leucine at codon 387 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |
Invitae | RCV003649178 | SCV001397920 | uncertain significance | Familial adenomatous polyposis 1 | 2023-09-03 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 387 of the APC protein (p.Leu387Val). This variant is present in population databases (rs760312726, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 818449). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function. 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. |
Gene |
RCV001843557 | SCV002102652 | uncertain significance | not provided | 2022-02-25 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with microsatellite unstable synchronous colorectal cancers and adenomas (Hanninen 2019); This variant is associated with the following publications: (PMID: 30894686) |