ClinVar Miner

Submissions for variant NM_001276345.2(TNNT2):c.720-6G>A (rs113471285)

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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 RCV000036613 SCV000060268 uncertain significance not specified 2014-07-31 criteria provided, single submitter clinical testing The 690-6G>A variant in TNNT2 has been identified by our laboratory in 1 Caucasi an individual with DCM (Morales 2010), who also carried a second TNNT2 variant o n the same copy of the gene (in cis). This variant was absent from large populat ion studies, but has been listed in dbSNP without frequency information (dbSNP r s113471285). This variant is located in the 3' splice region. Computational tool s do not suggest an impact to splicing. However, this information is not predict ive enough to rule out pathogenicity. In summary, the clinical significance of t he 690-6G>A variant is uncertain.
GeneDx RCV000036613 SCV000514926 benign not specified 2015-05-08 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 RCV000646081 SCV000767838 likely benign not provided 2018-11-02 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001099020 SCV001255428 uncertain significance Familial hypertrophic cardiomyopathy 2 2017-04-28 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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001099021 SCV001255429 uncertain significance Left ventricular noncompaction 6 2017-04-28 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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001099022 SCV001255430 uncertain significance Familial restrictive cardiomyopathy 3 2017-04-28 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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Color Health, Inc RCV001192357 SCV001360407 likely benign Cardiomyopathy 2019-10-22 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000036613 SCV001362089 uncertain significance not specified 2019-11-19 criteria provided, single submitter clinical testing Variant summary: TNNT2 c.690-6G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.6e-05 in 251442 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.690-6G>A has been reported in the literature in individuals affected with dilated- and hypertrophic cardiomyopathy (Morales_2010, Pugh_2014). These reports however, do not provide unequivocal conclusions about association of the variant with the disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and both of them classified the variant as benign (1x) or likely benign (1x). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Invitae RCV001426925 SCV001629588 likely benign Familial hypertrophic cardiomyopathy 2; Left ventricular noncompaction 6; Familial restrictive cardiomyopathy 3 2020-11-11 criteria provided, single submitter clinical testing

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