PVS1
This variant is a missense substitution, NP_000213.1:p.(Val50Leu), and does not fall into the generic PVS1 null-variant categories of nonsense, frameshift, or canonical +/-1,2 splice variants.
PS1
No reviewed evidence was identified showing that a different nucleotide change creates the same KIT p.(Val50Leu) amino acid substitution with an established pathogenic or likely pathogenic classification.
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 showing a damaging effect on KIT function.
PS4
Available evidence does not show that this variant is significantly enriched in affected individuals compared with controls.
PM1
This variant has not been shown to lie in a mutational hotspot or a well-established critical functional domain without benign variation.
PM3
No evidence was identified showing this variant in trans with a pathogenic variant in a recessive disease context.
PM5
No reviewed same-residue pathogenic or likely pathogenic comparator was established for KIT codon 50.
PM6
No assumed de novo occurrence without confirmed parentage was identified for this variant.
PP1
No segregation data were identified for this variant.
PP2
Available evidence does not establish that KIT meets PP2 requirements for a gene with a low rate of benign missense variation and a common pathogenic missense mechanism at a level suitable for criterion application.
PP3
Available computational evidence does not support a deleterious effect.
PP4
No phenotype information was provided that is sufficiently specific to apply PP4.
PP5
ClinVar shows mixed submissions and no expert-panel classification for this variant, so a reputable-source-only pathogenic assertion was not used.
