Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000204242 | SCV000259999 | pathogenic | Gorlin syndrome | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 10 of the PTCH1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PTCH1 are known to be pathogenic (PMID: 16301862, 16419085). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with basal cell nevus syndrome (BCNS) and/or PTCH1-related conditions (PMID: 16301862, 35437209; Invitae). This variant is also known as IVS10+1G>C. ClinVar contains an entry for this variant (Variation ID: 219879). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV000478859 | SCV000567004 | pathogenic | not provided | 2015-07-21 | criteria provided, single submitter | clinical testing | The c.1503+1 G>C splice site variant in the PTCH1 gene has been previously reported in association withGorlin syndrome (Klein et al., 2005). This variant destroys the canonical splice donor site in intron 10, and isexpected to cause abnormal gene splicing. Therefore, we consider the c.1503+1 G>C variant in PTCH1 as pathogenic. |