POLL Gene Curation

Gene-disease assertions not curated here (add link or write note): FROM HGMD (DM?): schizophrenia, head and neck squamous cell carcinoma, developmental disorder, congenital heart disease, prostate cancer). 1 DM duplication associated with autism

Disease
Inheritance	Autosomal recessive
Prevalence Possible sources Orphanet Medline Plus Genetics	N/A
Rapid or full curation?	Rapid Full
ClinGen / GenCC / BabySeq / HGMD	ClinGen - Dosage sensitivity curation: No evidence for triplosensitivity or haploinsufficiency. Tandem duplications that include LBX1, BTRC, and POLL, and had a breakpoint within FBXW4 (DAC) reported in individuals with split hand-foot malformation. GENCC - no curations HGMD - DM? Variants listed with several reported phenotypes (schizophrenia, head and neck squamous cell carcinoma, developmental disorder, congenital heart disease, prostate cancer). 1 DM duplication associated with autism. Did not review variants further.
Clinical Validity Scoring Notes and points	N/A
Clinical Validity Points Total	N/A
Clinical Validity Classification Classifications (pts) Definitive (12pts) Strong (12pts) Moderate (7-11pts) Limited (0.1-6pts) No genetic evidence Refuted Disputed	Limited/No Genetic Evidence
Molecular Mechanism Mechanisms Loss of function Gain of function Dominant negative Unknown Other	Loss of function / Gain of function / Dominant Negative
Penetrance options Complete (100%) High (≥90%) Reduced (<90% and >10%) Low (≤10%) (list source/PMID)	N/A
Age of Onset options Congenital Pediatric Adolescent Adulthood Late adulthood (list source/PMID)	N/A
Severity Options Embryonic lethal - presence of a pathogenic variant or variants is not compatible with life. The penetrance must be complete. Severe - presence of a pathogenic variant or variant(s) results in significantly reduced fitness. The penetrance must be complete or high. Moderate - significant morbidity or mortality due to clinical features, but fitness may not be reduced, or penetrance is reduced. Mild - Presence of a variant or variant(s) is not associated with reduced fitness, no significant morbidity or mortality, and/or penetrance is low. None - presence of a variant results in no phenotype. An example is recessive disorders in which no phenotype is reported in carriers.	N/A
Clinical Features	N/A
Gene SOPs & Notes	N/A
Curation Summary: Examples - The @GENE@ is associated with @inheritance pattern@ @condition@, which is characterized by @clinical features@ (PMIDs). - Variable expression or severity: The severity and expressivity of the disorder is highly variable, even within families. - If multiple conditions associated with the gene: It has also been associated with @inheritance pattern@ @condition@, which is characterized by @clinical features@ (PMIDs). - Limited evidence gene: The PCNA gene has been reported in individuals with early onset autosomal recessive ataxia (PMID: 33426167, 24911150), however, evidence supporting this gene-dsiease relationship is limited	N/A
Case ID, Curator name, Date, Jira ticket link	Andrea Oza, 06/14/2023 CIT-127 - Getting issue details... STATUS