Submissions for variant NM_003289.4(TPM2):c.782A>G (p.Tyr261Cys)

dbSNP: rs1824676022

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Breda Genetics srl	RCV001254895	SCV001426395	pathogenic	Arthrogryposis, distal, type 1A; Congenital myopathy 23	2020-07-28	criteria provided, single submitter	clinical testing	The variant c.782A>G (p.Tyr261Cys) in TPM2 has been reported by Beck et al. (2013) in a sporadic case of distal arthrogryposis type 2B (PMID: 23401156). The variant is reported as “affects function” in the Global Variome shared LOVD database v.3.0. This variant has not been reported in dbSNP, gnomAD, 1000 Genomes, NHLBI Exome Sequencing Project (ESP) or ClinVar. The nucleotide position is conserved across 35 mammalian species (GERP RS: 4.98).
GeneDx	RCV001573796	SCV002538760	pathogenic	not provided	2023-08-30	criteria provided, single submitter	clinical testing	Previously reported in the heterozygous state in two individuals with distal arthyrogryposis and/or congenital myopathy (Marttila et al., 2014); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23401156, 24692096)
Illumina Laboratory Services, Illumina	RCV003389253	SCV004101283	likely pathogenic	TPM2-related myopathy	2023-09-06	criteria provided, single submitter	clinical testing	The TPM2 c.782A>G (p.Tyr261Cys) missense variant has been identified in at least three individuals with congenital myopathy/distal arthrogryposis type 1, with at least one individual noted to have a de novo occurrence of the variant (PMID: 23401156; 24692096). This variant is not observed in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. Computational evidence suggests the variant may impact the gene or gene product. This variant has been shown to segregate with disease. Based on the available evidence, the c.782A>G (p.Tyr261Cys) variant is classified as likely pathogenic for TPM2-related myopathy.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001573796	SCV001800176	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001573796	SCV001956085	likely pathogenic	not provided		no assertion criteria provided	clinical testing