Submissions for variant NM_000367.5(TPMT):c.719A>G (p.Tyr240Cys)

gnomAD frequency: 0.04459  dbSNP: rs1142345

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000396233	SCV000331334	other	not provided	2015-07-21	criteria provided, single submitter	clinical testing
GeneDx	RCV000396233	SCV000977588	likely benign	not provided	2020-05-12	criteria provided, single submitter	clinical testing	Also known as TPMT*3C, Y240C is one of the most common TPMT variants (Katara and Kuntal, 2015; Iu et al., 2017); Published functional studies demonstrate a damaging effect, as measurement of enzymatic activity showed only 10% activity for Y240C (Iu et al., 2017); Individuals who receive conventional thiopurine doses and carry at least one TPMT *3C allele are at risk to experience myelosuppression. Thiopurine dosing guidelines based on TPMT genotype are available (Relling et al., 2013); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed on 3.7% (10506/282534 alleles) from individuals in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 27703193, 8561894, 15967990, 10591545, 25087612, 9695718, 18482735, 20970225, 26410243, 28462921, 8644731, 23422873, 31130284)
CeGaT Center for Human Genetics Tuebingen	RCV000396233	SCV005093675	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	TPMT: PM5, BS1, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV000396233	SCV005224988	likely benign	not provided		criteria provided, single submitter	not provided
OMIM	RCV000013562	SCV000033809	drug response	Thiopurine S-methyltransferase deficiency	2006-02-01	no assertion criteria provided	literature only