Submissions for variant NM_000363.5(TNNI3):c.244C>T (p.Pro82Ser)

gnomAD frequency: 0.00699  dbSNP: rs77615401

Total submissions: 28

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036277	SCV000059929	benign	not specified	2012-02-09	criteria provided, single submitter	clinical testing	Pro82Ser in exon 5 of TNNI3: This variant is classified as benign based on its h igh frequency in the general population (dbSNP rs77615401; NHLBI Exome Sequencin g Project, http://evs.gs.washington.edu/EVS). A=57/G=2853
GeneDx	RCV000224174	SCV000169016	benign	not provided	2018-12-13	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 23299917, 22995991, 25324519, 20981092, 18175163, 23967088, 11815426, 27150586, 21310275, 27532831, 26332594, 31006259)
Eurofins Ntd Llc (ga)	RCV000036277	SCV000230914	benign	not specified	2014-05-26	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000224174	SCV000280723	benign	not provided	2016-01-11	criteria provided, single submitter	clinical testing
Invitae	RCV000229361	SCV000284653	benign	Hypertrophic cardiomyopathy	2024-01-31	criteria provided, single submitter	clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000238609	SCV000296906	likely benign	Cardiomyopathy	2015-10-30	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000036277	SCV000303833	likely benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000252511	SCV000319864	benign	Cardiovascular phenotype	2015-06-25	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	RCV000271700	SCV000414756	likely benign	Familial restrictive cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000229361	SCV000414757	likely benign	Hypertrophic cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000367372	SCV000414758	likely benign	Dilated Cardiomyopathy, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000277490	SCV000414759	likely benign	Familial Hypertrophic Cardiomyopathy with Wolff-Parkinson-White Syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000224174	SCV000696594	benign	not provided	2016-08-09	criteria provided, single submitter	clinical testing	Variant Summary: The c.244C>T variant involves the alteration of a conserved nucleotide and 4/5 in silico tools predict a deleterious outcome. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.17%, predominantly observed in the African subpopulation at a frequency of 2.3% including 3 homozygous occurrences. This frequency exceeds the maximal expected allele frequency for a pathogenic variant in TNNI3 (0.0125%), suggesting this is a benign polymorphism found primarily in population(s) of African origin. The variant has been reported in the literature in HCM patients and controls, mostly of African descent. However, mouse model studies have suggested the variant to be a disease-modifying factor for dysfunction and adverse remodeling with aging and chronic pressure overload (Ramirez-Correa_2015), although the relationship of this finding to a monogenic causation is unclear, therefore the evidence is not weighed in its classification. Multiple reputable clinical labs have classified the variant as benign. Taken together, this variant is classified as Benign.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000224174	SCV000987343	benign	not provided		criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852767	SCV000995485	benign	Familial amyloid neuropathy; Cardiomyopathy	2019-06-03	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001133540	SCV001293244	likely benign	Dilated cardiomyopathy 2A	2018-04-05	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV001135028	SCV001294793	likely benign	Cardiomyopathy, familial restrictive, 1	2018-04-05	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000013233	SCV001294794	likely benign	Hypertrophic cardiomyopathy 7	2018-04-05	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000238609	SCV001333212	likely benign	Cardiomyopathy	2019-03-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000238609	SCV001350457	benign	Cardiomyopathy	2018-03-19	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000224174	SCV001471798	likely benign	not provided	2020-01-31	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002482859	SCV002796561	benign	Dilated cardiomyopathy 2A; Cardiomyopathy, familial restrictive, 1; Dilated cardiomyopathy 1FF; Hypertrophic cardiomyopathy 7	2022-04-18	criteria provided, single submitter	clinical testing
OMIM	RCV000013233	SCV000033480	risk factor	Hypertrophic cardiomyopathy 7	2008-07-01	no assertion criteria provided	literature only
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000224174	SCV001742484	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000224174	SCV001797733	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000036277	SCV001921672	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000036277	SCV001931510	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000036277	SCV001967717	benign	not specified		no assertion criteria provided	clinical testing