Submissions for variant NM_001330700.2(TOP2B):c.187C>T (p.His63Tyr)

dbSNP: rs886039770

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV005090302	SCV005834614	pathogenic	not provided	2024-11-17	criteria provided, single submitter	clinical testing	This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 58 of the TOP2B protein (p.His58Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with global developmental delay and intellectual disability (PMID: 28343847, 33644862). In at least one individual the variant was observed to be de novo. This variant is also known as c.187C>T (p.His63Tyr). ClinVar contains an entry for this variant (Variation ID: 265791). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects TOP2B function (PMID: 36450898). For these reasons, this variant has been classified as Pathogenic.
Clinics for Rare Diseases Referral (Hong Kong), The University of Hong Kong	RCV000256202	SCV000322735	likely pathogenic	Autism spectrum disorder	2016-10-11	no assertion criteria provided	clinical testing