Submissions for variant NM_000264.5(PTCH1):c.2561-1G>A

dbSNP: rs1131691700

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000493366	SCV000582656	pathogenic	not provided	2017-04-27	criteria provided, single submitter	clinical testing	The c.2561-1 G>A splice site variant in the PTCH1 gene destroys the canonical splice acceptor site in intron 15. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.2561-1 G>A variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).
Invitae	RCV003609154	SCV004428759	pathogenic	Gorlin syndrome	2023-01-09	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 429958). Disruption of this splice site has been observed in individuals with basal cell nevus syndrome (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 15 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).
MutSpliceDB: a database of splice sites variants effects on splicing, NIH	RCV000493366	SCV000925693	not provided	not provided		no assertion provided	in vitro