Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000123042 | SCV000166337 | benign | Gorlin syndrome | 2024-12-12 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002362751 | SCV002656905 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-16 | criteria provided, single submitter | clinical testing | The p.M216V variant (also known as c.646A>G), located in coding exon 4 of the PTCH1 gene, results from an A to G substitution at nucleotide position 646. The methionine at codon 216 is replaced by valine, an amino acid with highly similar properties. This amino acid position is 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004998248 | SCV005623763 | uncertain significance | not provided | 2024-08-28 | criteria provided, single submitter | clinical testing | The PTCH1 c.646A>G (p.Met216Val) variant has been reported in the published literature in an individual with early onset breast cancer ((PMID: 35957908 (2022)). The frequency of this variant in the general population, 0.000098 (3/30610 chromosomes in South Asian subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |