PS1
Not assessed: no validated pathogenic MSH3 comparator producing the same amino-acid change, p.Ala44Gly, was identified.
PS2
Not assessed: no parental genotypes or confirmed de novo observation are documented for the affected proband.
PS3
Not assessed: no variant-specific validated functional assay with appropriate controls was identified for MSH3 p.(Ala44Gly).
PS4
Not assessed: no exact-variant case-control counts, enrichment statistic, or statistically supported affected-case series were available.
PM1
Not assessed: no authoritative MSH3 domain table was retrieved, and the A44 hotspot query found no statistically significant hotspot.
PM3
Not assessed: no affected individual, second pathogenic allele, phase, or biallelic MSH3 observation is documented for c.131C>G.
PM5
Not assessed: zero eligible pathogenic missense comparators were identified at MSH3 residue 44.
PM6
Not assessed: no clinical report or family-history evidence supports a presumed de novo event without parental testing.
PP1
Not assessed: no informative affected relatives, familial variant testing, or meiosis count is documented for segregation analysis.
PP2
Not assessed: MSH3 loss-of-function support does not establish the gene-level missense enrichment required for PP2.
PP3
Not met: missense REVEL score 0.138 is below the >=0.644 supporting PP3 threshold.
PP4
Not assessed: no patient phenotype, family history, or disease-specific clinical presentation was provided to evaluate phenotype specificity.
PP5
Not met: ClinVar shows 0 expert-panel submissions for the exact variant, with available laboratory assertions classified as uncertain significance or likely benign.
