ClinVar Miner

Submissions for variant NM_001083602.2(PTCH1):c.869+5G>C (rs372657547)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000230634 SCV000284307 uncertain significance Gorlin syndrome 2018-12-04 criteria provided, single submitter clinical testing This sequence change falls in intron 7 of the PTCH1 gene. It does not directly change the encoded amino acid sequence of the PTCH1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs372657547, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with PTCH1-related disease. ClinVar contains an entry for this variant (Variation ID: 237448). Nucleotide substitutions within 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 is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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.
GeneDx RCV000414676 SCV000491382 uncertain significance not provided 2016-01-07 criteria provided, single submitter clinical testing The c.1067+5 G>C variant has not been published as a pathogenic variant, nor has it been reported asa benign variant to our knowledge. It was not observed with any significant frequency inapproximately 6,500 individuals of European and African American ancestry in the NHLBI ExomeSequencing Project. Several in-silico splice prediction models predict that c.1067+5 G>C may damagethe natural splice donor site for IVS7 and lead to abnormal gene splicing. However, in the absence ofRNA/functional studies, the actual effect of this sequence change in this individual is unknown.Therefore, based on the currently available information, it is unclear whether this variant is apathogenic variant or a rare benign variant
Ambry Genetics RCV000492679 SCV000581073 likely benign Hereditary cancer-predisposing syndrome 2018-03-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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