ClinVar Miner

Submissions for variant NM_000364.4(TNNT2):c.411+6T>A (rs761043932)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768724 SCV000900094 uncertain significance Cardiomyopathy 2016-01-07 criteria provided, single submitter clinical testing
Color RCV000768724 SCV000907043 uncertain significance Cardiomyopathy 2018-06-11 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This variant changes a single nucleotide in intron 9 of the TNNT2 gene. Computational splicing tools suggest that this variant may impact the RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in an individual affected with cardiovascular disorders in the literature. This variant has been identified in 4/277188 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Invitae RCV000815232 SCV000955680 uncertain significance Familial hypertrophic cardiomyopathy 2; Left ventricular noncompaction 6; Familial restrictive cardiomyopathy 3 2018-08-21 criteria provided, single submitter clinical testing This sequence change falls in intron 9 of the TNNT2 gene. It does not directly change the encoded amino acid sequence of the TNNT2 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs761043932, ExAC 0.001%). This variant has not been reported in the literature in individuals with TNNT2-related disease. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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