PS1
No evidence was identified showing that another nucleotide change creates the same amino acid substitution with an established pathogenic classification, so PS1 was not assessed.
PS2
No confirmed de novo occurrence with parental testing was identified for this variant, so PS2 was not assessed.
PS3
No well-established functional study for this exact variant was identified that demonstrates a damaging effect, so PS3 was not assessed.
PS4
Available evidence does not show enrichment of this variant in affected individuals compared with controls.
PM1
This variant has not been shown to lie in a well-established mutational hotspot or critical functional domain without benign variation.
PM2
This variant is not absent or rare in population databases.
PM3
No evidence was identified regarding occurrence of this variant in trans with a pathogenic variant in a recessive disease context, so PM3 was not assessed.
PM6
No probable de novo occurrence without full parental confirmation was identified for this variant, so PM6 was not assessed.
PP1
No segregation data were identified for this variant, so PP1 was not assessed.
PP2
No gene-specific evidence was identified showing that TERT is a gene in which pathogenic missense variation is the predominant disease mechanism with a low rate of benign missense variation, so PP2 was not assessed.
PP3
Available computational evidence does not support a damaging effect.
PP4
No phenotype data specific enough to show that the individual's presentation is highly specific for a TERT-related disorder were identified, so PP4 was not assessed.
PP5
PP5 was not used because no qualifying reputable-source pathogenic assertion independent of the underlying evidence review was identified.
