PS1
No evidence was identified that another nucleotide change produces the same amino acid substitution with an established pathogenic classification, so PS1 cannot be applied from the available data.
PS2
No confirmed de novo occurrence was identified.
PS3
No well-established functional study of this exact variant was identified showing a damaging effect on lipoprotein lipase function, so PS3 is not applied.
PS4
The available data do not show a statistically increased prevalence of this variant in affected individuals compared with controls, so PS4 cannot be applied.
PM1
This variant has not been shown to lie in a statistically significant hotspot or other well-established critical functional region without benign variation, so PM1 is not met.
PM3
No evidence was identified that this variant was observed in trans with a pathogenic variant in an affected individual, so PM3 cannot be assessed from the available data.
PM5
No evidence was identified for a different pathogenic missense change at codon 462, so PM5 cannot be applied from the available data.
PM6
No assumed de novo occurrence without confirmed parentage was identified, so PM6 is not applied.
PP1
No segregation data were identified showing that this variant tracks with LPL-related disease in a family, so PP1 cannot be applied.
PP2
Available evidence does not establish a gene-specific pattern that would support applying PP2 to this missense variant.
PP4
No case-specific phenotype information was provided that is sufficiently specific for an LPL-related disorder, so PP4 cannot be assessed.
