ClinVar Miner

Submissions for variant NM_000264.5(PTCH1):c.945+3_945+6del

dbSNP: rs1064795637
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479558 SCV000571627 likely pathogenic not provided 2016-12-14 criteria provided, single submitter clinical testing This variant is denoted PTCH1 c.945+3_945+6delGAGT or IVS6+3_IVS6+6delGAGT and consists of a deletion of four nucleotides at the +3 to +6 position in intron 6 of the PTCH1 gene. The normal sequence with the bases that are deleted in braces is AAGT[GAGT]ACCA. Multiple in silico models predict this variant to destroy the nearby natural donor site, and to possibly cause abnormal gene splicing. PTCH1 c.945+3_945+6delGAGT was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. The deleted nucleotides include one that is conserved across species, one that is conserved through mammals and two that are not conserved. Based on the currently available information, we consider PTCH1 c.945+3_945+6delGAGT to be a likely pathogenic variant.
Invitae RCV003502531 SCV004307315 uncertain significance Gorlin syndrome 2023-08-27 criteria provided, single submitter clinical testing This sequence change falls in intron 6 of the PTCH1 gene. It does not directly change the encoded amino acid sequence of the PTCH1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PTCH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 422218). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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