Submissions for variant NM_006757.4(TNNT3):c.187C>T (p.Arg63Cys)

dbSNP: rs199474721

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000194279	SCV000249170	pathogenic	Arthyrgryposis, distal, type 2B	2015-07-01	criteria provided, single submitter	clinical testing
SIB Swiss Institute of Bioinformatics	RCV000787280	SCV000996474	likely pathogenic	Arthrogryposis, distal, type 2B2	2019-08-22	criteria provided, single submitter	curation	This variant is interpreted as a Likely pathogenic for Arthrogryposis, distal, 2B2, autosomal dominant. The following ACMG Tag(s) were applied: PM2, PP3, PP1, PM5.
GeneDx	RCV000024570	SCV001813516	pathogenic	not provided	2021-12-10	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 31230720, 23401156, 21402185, 26774798, 34766372, 33977145)
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	RCV000787280	SCV002817385	likely pathogenic	Arthrogryposis, distal, type 2B2	2022-12-15	criteria provided, single submitter	clinical testing	A heterozygous missense variation in exon 10 of the TNNT3 gene that results in the amino acid substitution of Cysteine for Arginine at codon 63 (p.Arg63Cys) was detected . The observed variation has previously been reported in patients affected with distal arthrogryposis [PMID:21402185]. This variant has not been reported in the 1000 genomes, gnomAD databases. The in silico predictions of the variant are probably damaging by PolyPhen-2 (HumDiv) and damaging by SIFT, LRT and MutationTaster2. The reference codon is conserved across mammals. In summary, the variant meets our criteria to be classified as likely pathogenic.
Leiden Muscular Dystrophy (TNNT3)	RCV000024570	SCV000045874	not provided	not provided	2012-03-18	no assertion provided	curation
OMIM	RCV000787280	SCV000914181	pathogenic	Arthrogryposis, distal, type 2B2	2011-05-01	no assertion criteria provided	literature only
Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust	RCV000787280	SCV000926212	pathogenic	Arthrogryposis, distal, type 2B2	2019-05-03	no assertion criteria provided	clinical testing
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000787280	SCV001167516	uncertain significance	Arthrogryposis, distal, type 2B2		no assertion criteria provided	research