PVS1
NF1 loss of function is an established disease mechanism, but this variant is an in-frame protein-altering delins rather than a nonsense, frameshift, or canonical splice-site variant, and SpliceAI predicts no significant splice impact (max delta score 0.01).
PS1
No evidence was identified showing that this variant produces the same amino acid change as a previously established pathogenic variant.
PS2
No confirmed de novo occurrence with parental confirmation was identified for this variant.
PS3
No well-established functional study for this exact variant was identified, so functional evidence supporting a damaging effect is not available.
PS4
No enrichment data, case-control evidence, or count of multiple unrelated affected individuals with this exact variant was identified.
PM1
Available evidence does not show that this variant lies in an established NF1 mutational hotspot or a critical functional domain without benign variation.
PM4
This variant results in an in-frame amino acid substitution-delins, p.(Phe2697_Ser2698delinsValLeu), without a net protein length change, so available evidence does not support PM4.
PM6
No assumed de novo occurrence without full parental confirmation was identified for this variant.
PP1
No segregation data were identified for this variant, so cosegregation with disease cannot be assessed.
PP3
SpliceAI predicts no significant splice impact for this variant, with a maximum delta score of 0.01.
PP4
No phenotype information was provided that would allow assessment of whether the observed clinical presentation is highly specific for an NF1-related disorder caused by this gene.
PP5
No reputable source classification for this exact variant was identified in the reviewed materials.
