ClinVar Miner

Submissions for variant NM_000364.3(TNNT2):c.113C>T (p.Ala38Val) (rs200754249)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000036624 SCV000060279 benign not specified 2018-03-15 criteria provided, single submitter clinical testing p.Ala28Val in exon 5 of TNNT2: This variant is classified as benign because it h as been identified in 0.07% (84/126672) of European chromosomes by the Genome Ag gregation Database (gnomAD,; dbSNP rs200754249) . Furthermore, alanine (Ala) at position 28 is not conserved in mammals or evolu tionarily distant species and >10 mammals carry a valine (Val) at this position, supporting that this change may be tolerated. ACMG/AMP Criteria applied: BS1; B P4_Strong.
CSER_CC_NCGL; University of Washington Medical Center RCV000148900 SCV000190646 uncertain significance Increased left ventricular wall thickness 2014-06-01 criteria provided, single submitter research Low GERP score may suggest that this variant may belong in a lower pathogenicity class
GeneDx RCV000036624 SCV000209275 likely benign not specified 2018-03-07 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.
Invitae RCV000456645 SCV000541927 likely benign Familial hypertrophic cardiomyopathy 2; Left ventricular noncompaction 6; Familial restrictive cardiomyopathy 3 2017-11-27 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588568 SCV000697571 likely benign not provided 2016-10-25 criteria provided, single submitter clinical testing Variant summary: The TNNT2 c.83C>T (p.Ala28Val) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 60/126398 control chromosomes, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.0006453 (43/66632). This frequency is about 3 times the estimated maximal expected allele frequency of a pathogenic TNNT2 variant (0.00025), suggesting this is likely a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. One internal sample also carried a pathogenic variant in MYBPC3 c.2308G>A/p.D770N and LMM cites the variant to co-occur in a patient with an unspecified pathogenic variant in another gene known to cause HCM, further supporting the non-pathogenicity of this variant. This variant has been reported in HCM and DCM patients without strong evidence for causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as VUS/likely benign. LMM has classified the variant as likely benign, in part because of unpublished data from their lab showing the variant did not segregate with disease in 2 affected relatives from one family with DCM. Taken together, this variant is classified as likely benign until more evidence becomes available.
Equipe Genetique des Anomalies du Developpement,Université de Bourgogne RCV000755701 SCV000883135 uncertain significance Left ventricular noncompaction 6 2018-11-21 criteria provided, single submitter clinical testing
Color RCV000771256 SCV000903366 likely benign Cardiomyopathy 2018-06-18 criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852592 SCV000995294 likely benign Supraventricular tachycardia 2017-10-02 criteria provided, single submitter clinical testing
Evolutionary and Medical Genetics Laboratory, Centre for Cellular and Molecular Biology RCV000149450 SCV000196094 pathogenic Primary familial hypertrophic cardiomyopathy no assertion criteria provided not provided Converted during submission to Pathogenic.

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