Submissions for variant NM_001276345.2(TNNT2):c.788A>G (p.Lys263Arg)

gnomAD frequency: 0.05965  dbSNP: rs3730238

Total submissions: 22

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000172779	SCV000051611	benign	Primary familial hypertrophic cardiomyopathy	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036617	SCV000060272	benign	not specified	2008-01-18	criteria provided, single submitter	clinical testing
GeneDx	RCV000036617	SCV000169024	benign	not specified	2011-07-14	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.
PreventionGenetics, part of Exact Sciences	RCV000036617	SCV000305600	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000254202	SCV000317815	benign	Cardiovascular phenotype	2015-07-02	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
Illumina Laboratory Services, Illumina	RCV000300748	SCV000353316	likely benign	Familial restrictive cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000336926	SCV000353317	likely benign	Left ventricular noncompaction cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000403500	SCV000353318	likely benign	Dilated Cardiomyopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000297085	SCV000353319	likely benign	Hypertrophic cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588643	SCV000697568	benign	not provided	2016-08-24	criteria provided, single submitter	clinical testing	Variant summary: The TNNT2 c.758A>G (p.Lys253Arg) variant involves the alteration of a conserved nucleotide. 3/3 in silico tools predict a benign outcome for this variant. This variant was found in 6169/122538 control chromosomes (378 homozygotes) at a frequency of 0.0503436, which is approximately 288 times the estimated maximal expected allele frequency of a pathogenic TNNT2 variant (0.000175), suggesting this variant is likely a benign polymorphism. In literature, this variant has been reported as a polymorphism found in HCM patients as well as healthy controls (Watkins_1995, Torricelli_2003, Garcia_Castro_2007, etc.). It has also been found to not cosegregate with disease in HCM families (Watkins_1995). In a mammalian two-hybrid assay, L253R mutant did not affect on interactions between TnT and TnI or TnT and TnC (Mogensen_2004). In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as benign. Taken together, this variant is classified as Benign.
Color Diagnostics, LLC DBA Color Health	RCV000771068	SCV000902586	benign	Cardiomyopathy	2018-03-15	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000588643	SCV000987477	benign	not provided		criteria provided, single submitter	clinical testing
Invitae	RCV001083231	SCV001000591	benign	Hypertrophic cardiomyopathy 2; Dilated cardiomyopathy 1D; Cardiomyopathy, familial restrictive, 3	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003450718	SCV004180539	likely benign	Dilated cardiomyopathy 1D	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003450719	SCV004180540	likely benign	Cardiomyopathy, familial restrictive, 3	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003450717	SCV004180541	likely benign	Hypertrophic cardiomyopathy 2	2023-04-11	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000771068	SCV004821971	benign	Cardiomyopathy	2024-02-05	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000036617	SCV001920100	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000036617	SCV001931076	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000036617	SCV001954430	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000036617	SCV001968877	benign	not specified		no assertion criteria provided	clinical testing
Cohesion Phenomics	RCV000771068	SCV003803070	benign	Cardiomyopathy	2022-10-10	no assertion criteria provided	clinical testing