Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001015535 | SCV001176380 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-06-19 | criteria provided, single submitter | clinical testing | The c.2438_2446dupCGAATATCC variant (also known as p.P813_I815dup), located in coding exon 15 of the PTCH1 gene, results from an in-frame duplication of CGAATATCC at nucleotide positions 2438 to 2446. This results in the duplication of 3 extra residues (PNI) between codons 813 and 815. This alteration has been reported in individuals with personal and family history consistent with Nevoid Basal Cell Carcinoma Syndrome (Johnson RL et al. Science, 1996 Jun;272:1668-71; Ambry Internal Data). This amino acid region is not well conserved in available vertebrate species. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Invitae | RCV001072024 | SCV001237367 | likely pathogenic | Gorlin syndrome | 2021-10-11 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 821274). This variant is also known as an insertion of 9 base pairs at nucleotide 2445. This variant has been observed in individuals with basal cell nevus syndrome (PMID: 8658145; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). This variant, c.2438_2446dup, results in the insertion of 3 amino acid(s) to the PTCH1 protein (p.Pro813_Ile815dup), but otherwise preserves the integrity of the reading frame. |
| Prevention |
RCV003928662 | SCV004743745 | pathogenic | PTCH1-related condition | 2023-10-26 | criteria provided, single submitter | clinical testing | The PTCH1 c.2438_2446dup9 variant is predicted to result in an in-frame duplication (p.Pro813_Ile815dup). This variant was reported in an individual with basal cell nevus syndrome, and segregated with disease in two additional affected and three unaffected family members (described as occurring at nucleotide 2445, Johnson et al 1996. PubMed ID: 8658145). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating it is rare. In ClinVar, this variant is interpreted as pathogenic and likely pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/variation/821274/). This variant is interpreted as pathogenic. |
| OMIM | RCV001072024 | SCV000028903 | pathogenic | Gorlin syndrome | 1996-06-14 | no assertion criteria provided | literature only |