PS1
Not assessed: no alternate codon producing p.Arg11Trp with an established pathogenic classification was identified.
PS2
Not assessed: no parental genotypes, parentage confirmation, or de novo observations for p.Arg11Trp were available.
PS3
Not assessed: no functional assay results (e.g., glycosylase activity or DNA repair assays) for p.Arg11Trp were available.
PS4
Not assessed: no case-control counts, odds ratio, or affected-case series for p.Arg11Trp were available.
PM1
Not assessed: no NTHL1 domain-boundary or hotspot annotation was available, and CancerHotspots reported no significant hotspot at residue 11.
PM3
Not assessed: no affected individual with p.Arg11Trp in trans with a pathogenic NTHL1 variant was reported.
PM5
Not assessed: no alternate missense change at Arg11 with an established pathogenic classification was identified.
PM6
Not assessed: no de novo occurrence with unconfirmed parental testing was reported.
PP1
Not assessed: no pedigree or affected-relative genotype data were available to evaluate co-segregation.
PP2
Not assessed: NTHL1 disease is driven by biallelic loss-of-function variants, and no missense-constraint metric was available to assess benign missense rate.
PP3
Not met: REVEL score 0.196 falls below the 0.250 BP4 threshold, not above the 0.750 PP3 threshold.
PP4
Not assessed: no individual-level phenotype or tumor data were provided.
PP5
Not met: ClinVar holds only non-expert Uncertain significance submissions, with no expert-panel Pathogenic or Likely pathogenic assertion.
