Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000558601 | SCV000622990 | likely benign | Gorlin syndrome | 2024-11-04 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002323898 | SCV002607108 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-04 | criteria provided, single submitter | clinical testing | The p.V1116M variant (also known as c.3346G>A), located in coding exon 20 of the PTCH1 gene, results from a G to A substitution at nucleotide position 3346. The valine at codon 1116 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |
| St. |
RCV000558601 | SCV003928113 | uncertain significance | Gorlin syndrome | 2023-04-18 | criteria provided, single submitter | clinical testing | The PTCH1 c.3346G>A (p.Val1116Met) missense change has a maximum subpopulation frequency of 0.00088% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with nevoid basal cell carcinoma syndrome. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
| Baylor Genetics | RCV003459158 | SCV004206584 | uncertain significance | Basal cell carcinoma, susceptibility to, 1 | 2023-08-18 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004800444 | SCV005423585 | uncertain significance | not specified | 2024-10-01 | criteria provided, single submitter | clinical testing | Variant summary: PTCH1 c.3346G>A (p.Val1116Met) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.1e-06 in 1607118 control chromosomes, predominantly at a frequency of 1.1e-05 within the Non-Finnish European subpopulation in the gnomAD database (v4.1 dataset). This frequency is somewhat lower than the estimated maximum expected for a pathogenic variant in PTCH1 causing Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome) (1.7e-05), allowing no clear conclusions about variant significance. To our knowledge, no occurrence of c.3346G>A in individuals affected with Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome) and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 453848). Based on the evidence outlined above, the variant was classified as uncertain significance. |