Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000708955 | SCV000838082 | uncertain significance | Familial adenomatous polyposis 1 | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001013445 | SCV001174029 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-10 | criteria provided, single submitter | clinical testing | The p.Y622H variant (also known as c.1864T>C), located in coding exon 14 of the APC gene, results from a T to C substitution at nucleotide position 1864. The tyrosine at codon 622 is replaced by histidine, an amino acid with similar properties. This alteration was detected in a cohort of 1663 Brazilian breast cancer patients who underwent hereditary multigene panel testing (Guindalini RSC et al. Sci Rep, 2022 Mar;12:4190). This amino acid position is well conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004997220 | SCV005622686 | uncertain significance | not provided | 2024-01-26 | criteria provided, single submitter | clinical testing | The APC c.1864T>C (p.Tyr622His) variant has not been reported in individuals with APC-related conditions in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |