Submissions for variant NM_001032283.3(TMPO):c.565+2487C>T

gnomAD frequency: 0.00576  dbSNP: rs17028450

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000172599	SCV000054804	likely benign	Primary dilated cardiomyopathy	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037751	SCV000061413	benign	not specified	2012-10-19	criteria provided, single submitter	clinical testing	Arg690Cys in exon 4 of TMPO: This variant is not expected to have clinical signi ficance because it has been identified in 11.7% (15/128) of Mexican American chr omosomes from a broad population by the 1000 Genomes project (dbSNP rs17028450). This variant has been previously reported in 2 siblings with DCM (Taylor 2005).
Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center	RCV000013544	SCV000267531	uncertain significance	Dilated cardiomyopathy 1T	2016-03-18	criteria provided, single submitter	reference population
Invitae	RCV000231421	SCV000287931	benign	Loeys-Dietz syndrome 2	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002310628	SCV000318751	benign	Inborn genetic diseases	2015-09-18	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx	RCV000037751	SCV000514912	benign	not specified	2017-02-20	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001810855	SCV001159171	benign	not provided	2023-11-22	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001258228	SCV001435130	benign	Hypertrophic cardiomyopathy 25		criteria provided, single submitter	research	The heterozygous p.Arg690Cys variant in TCAP has been identified in at least 2 siblings with dilated cardiomyopathy (PMID: 16247757). In vitro functional studies provide some evidence that the p.Arg690Cys variant may slightly impact protein function (PMID: 16247757). However, these types of assays may not accurately represent biological function. This variant is classified as benign for autosomal dominant dilated cardiomyopathy because it has been identified in >14% of Latino chromosomes and 141 total homozygotes by ExAC (http://gnomad.broadinstitute.org/).
PreventionGenetics, part of Exact Sciences	RCV003904834	SCV004723430	benign	TMPO-related condition	2019-07-10	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
OMIM	RCV000013544	SCV000033791	uncertain significance	Dilated cardiomyopathy 1T	2005-12-01	no assertion criteria provided	literature only
Stanford Center for Inherited Cardiovascular Disease, Stanford University	RCV000037751	SCV000280496	benign	not specified	2014-09-16	no assertion criteria provided	clinical testing	Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. p.Arg690Cys (c.2068 C>T) in TMPO (NM_003276.2) This variant has been seen previously with DCM (Taylor et al 2005). However, it was also seen in 13 of 60 indiviudals of Mexican ancestry in 1000 genomes including two homozygous individuals. Our team recently reviewed the evidence that TMPO is implicated in cardiomyopathy and found it to be weak.