PVS1
This variant is a missense substitution, p.(Gly1163Asp), and does not fall into the generic PVS1 null-variant categories of nonsense, frameshift, or canonical +/-1,2 splice variants.
PS1
No evidence was identified that this exact amino acid change, p.(Gly1163Asp), is caused by a different nucleotide change already established as pathogenic.
PS2
No confirmed de novo occurrence with verified maternity and paternity was identified for this variant.
PS3
No well-established functional study of this exact variant was identified, so pathogenic functional evidence could not be assessed.
PS4
Available evidence does not show enrichment of this variant in affected individuals compared with controls.
PM1
This variant does not have evidence of occurring in a well-established mutational hotspot or a clearly defined critical functional domain without benign variation.
PM2
This variant is not absent or rare in population databases.
PM3
No evidence was identified showing this variant in trans with a pathogenic variant in a recessive disease setting.
PM5
No evidence was identified that a different missense change at codon 1163 is already established as pathogenic.
PM6
No presumed de novo occurrence of this variant without confirmed parentage was identified.
PP1
No segregation data were identified for this variant, so co-segregation with disease could not be assessed.
PP2
No gene-specific evidence was identified showing that pathogenic missense variation is a common mechanism in MLH3 and that benign missense variation is uncommon, so PP2 was not assessed.
PP3
Available computational evidence does not support a deleterious effect.
PP4
No highly specific phenotype, family history, or tumor profile attributable to this exact variant was identified, so PP4 could not be assessed.
PP5
A pathogenic assertion from a reputable source without accessible supporting evidence was not identified for this variant.
