PS1
Not assessed: no pathogenic variant producing the identical amino acid change (p.His739Phe) via a different nucleotide was available for comparison.
PS2
Not assessed: no parental genotype or maternity/paternity data were available to establish a de novo occurrence.
PS3
Not assessed: no functional assay evidence (e.g., minigene, reporter) for this specific variant was identified in the literature.
PS4
Not assessed: no case series or case-control enrichment data showed an excess of this exact variant in affected individuals.
PM1
Not assessed: no PTCH1 domain or hotspot annotation for residue 739 was available; the somatic cancer hotspot query returned no hit.
PM3
Not assessed: no biallelic evidence or second pathogenic allele was documented to support recessive inheritance.
PM5
Not assessed: no different pathogenic missense variant at the same residue (position 739) was identified for comparison.
PM6
Not assessed: no suspected de novo occurrence or parental testing data were available.
PP1
Not assessed: no segregation data from affected or unaffected relatives were documented.
PP2
Not assessed: no missense constraint metrics were available to determine whether missense is a common disease mechanism in PTCH1.
PP3
Not met: SpliceAI max delta 0.002 is far below the 0.2 high-recall threshold, and no calibrated missense predictor output was available.
PP4
Not assessed: no patient phenotype or clinical diagnostic criteria were available to link the variant to the phenotype.
PP5
Not met: the ClinVar record has zero expert-panel submissions, so no expert-panel classification supports pathogenicity.
