ClinVar Miner

Submissions for variant NM_001083602.2(PTCH1):c.387-1G>C (rs1057520590)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000442382 SCV000516185 pathogenic not provided 2015-04-04 criteria provided, single submitter clinical testing The c.585-1G>C variant in the PTCH1 gene has not been reported previously as a pathogenic variant nor as a benign polymorphism, to our knowledge. This splice site variant destroys the canonicalsplice acceptor site in intron 3. It is predicted to cause abnormal gene splicing, either leading to anabnormal 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.585-1G>C variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. While the c.585-1G>C variant has not previously been described, another splice site variant in the same position (c.585-1G>A) has been reported in association with a PTCH1-related disorder (Pastorino, et al., 2012). We interpret c.585-1G>C as a pathogenic variant.
Invitae RCV000558322 SCV000623050 pathogenic Gorlin syndrome 2017-02-28 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 3 of the PTCH1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with a PTCH1-related disease. A different splice site variant affecting this nucleotide (c.585-1G>A) has been observed in two families affected with nevoid basal cell carcinoma syndrome, also known as Gorlin syndrome (PMID: 22952776, 24816767). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.

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