ClinVar Miner

Submissions for variant NM_000264.5(PTCH1):c.1348-2A>G

dbSNP: rs1064793978
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486543 SCV000567496 pathogenic not provided 2015-08-05 criteria provided, single submitter clinical testing The IVS9-2 A>G splice site variant in the PTCH1 gene has been previously reported in association withGorlin syndrome (Pastorino et al., 2012). This substitution destroys the canonical splice acceptor site in intron 9, and is expected to cause abnormal gene splicing. Therefore, we interpret IVS9-2 A>G as a pathogenic variant.
Invitae RCV001385525 SCV001585407 pathogenic Gorlin syndrome 2020-06-01 criteria provided, single submitter clinical testing This variant has been observed in individual(s) with nevoid basal cell carcinoma syndrome (NBCCS) (PMID: 22952776, 29277811). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 419592). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 9 of the PTCH1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants 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).

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