Submissions for variant NM_000264.5(PTCH1):c.822del (p.Val275fs)

dbSNP: rs1554699964

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000657376	SCV000779109	pathogenic	not provided	2017-08-25	criteria provided, single submitter	clinical testing	This deletion of one nucleotide in PTCH1 is denoted c.822delA at the cDNA level and p.Val275TrpfsX8 (V275WfsX8) at the protein level. The normal sequence, with the base that is deleted in brackets, is ATCA[delA]GTGG. The deletion causes a frameshift which changes a Valine to a Tryptophan at codon 275, and creates a premature stop codon at position 8 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Invitae	RCV001386213	SCV001586352	pathogenic	Gorlin syndrome	2023-06-23	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 545818). This variant has not been reported in the literature in individuals affected with PTCH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val275Trpfs*8) in the PTCH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PTCH1 are known to be pathogenic (PMID: 16301862, 16419085).