ClinVar Miner

Submissions for variant NM_000264.5(PTCH1):c.394+6_394+17del

gnomAD frequency: 0.00001  dbSNP: rs774338309
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001362744 SCV001558777 benign Gorlin syndrome 2023-12-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003399166 SCV004121986 uncertain significance not specified 2023-10-23 criteria provided, single submitter clinical testing Variant summary: PTCH1 c.394+6_394+17del12 alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8.3e-06 in 240296 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.394+6_394+17del12 in individuals affected with Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome) and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV004998852 SCV005623767 uncertain significance not provided 2024-01-24 criteria provided, single submitter clinical testing The PTCH1 c.394+6_394+17del variant has not been reported in individuals with PTCH1-related conditions in the published literature. The frequency of this variant in the general population, 0.0000083 (2/240296 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on splicing yielded predictions that this variant does not affect PTCH1 mRNA splicing. Based on the available information, we are unable to determine the clinical significance of this variant.

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