Submissions for variant NM_001018005.2(TPM1):c.184G>C (p.Glu62Gln)

dbSNP: rs199476305

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Human Genetics, University of Leuven	RCV000768494	SCV000886799	likely pathogenic	Hypertrophic cardiomyopathy	2018-10-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004686570	SCV005178971	likely pathogenic	Cardiovascular phenotype	2024-03-18	criteria provided, single submitter	clinical testing	The p.E62Q variant (also known as c.184G>C), located in coding exon 2 of the TPM1 gene, results from a G to C substitution at nucleotide position 184. The glutamic acid at codon 62 is replaced by glutamine, an amino acid with highly similar properties. This missense alteration is located in a region that has a low rate of benign missense variation (Lek M et al. Nature. 2016 Aug 18;536(7616):285-91; DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources. Firth H.V. et al. 2009. Am.J.Hum.Genet. 84, 524-533 (DOI:dx.doi.org/10/1016/j.ajhg.2009.03.010)). This variant was reported in multiple individuals with features consistent with hypertrophic (HCM), dilated cardiomyopathy (DCM) or unspecified cardiomyopathy, and segregated with disease in a family with HCM and sudden death (Jongbloed RJ et al. J Am Coll Cardiol, 2003 Mar;41:981-6; Te Rijdt WP et al. Cardiovasc Pathol, 2017 May;30:23-26; Robyns T et al. Eur J Med Genet, 2020 Mar;63:103754; Stroeks SLVM et al. Genet Med, 2021 Nov;23:2186-2193). Functional studies indicate this variant may impact protein function; however, additional evidence is needed to confirm these findings (Chang AN et al. Front Physiol, 2014 Dec;5:460; Dorsch LM et al. Int J Cardiol, 2021 Jan;323:251-258; Farman GP et al. Arch Biochem Biophys, 2018 Jun;647:84-92). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Leiden Muscular Dystrophy (TPM1)	RCV000024572	SCV000045878	not provided	not provided	2012-04-15	no assertion provided	curation
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000024572	SCV001739879	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000024572	SCV001917189	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000024572	SCV001952318	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000024572	SCV001970223	pathogenic	not provided		no assertion criteria provided	clinical testing