ClinVar Miner

Submissions for variant NM_001276345.2(TNNT2):c.852-2A>C (rs111692981)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484808 SCV000566974 pathogenic not provided 2015-06-19 criteria provided, single submitter clinical testing Although the c.822-2 A>C substitution has not been reported as a pathogenic variant or as a benignpolymorphism to our knowledge, this variant destroys the canonical splice acceptor site in intron 15 and ispredicted to cause abnormal gene splicing. The variant is predicted to lead to either an abnormal messagethat is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message isused for protein translation. Other splice site variants in the TNNT2 gene have been reported in HGMDin association with cardiomyopathy (Stenson P et al., 2014). In summary, c.822-2 A>C in the TNNT2 gene is interpreted as a pathogenic variant.
Ambry Genetics RCV000618372 SCV000740250 uncertain significance Cardiovascular phenotype 2017-11-28 criteria provided, single submitter clinical testing The c.822-2A>C intronic variant results from an A to C substitution two nucleotides upstream from coding exon 16 in the TNNT2 gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice acceptor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. However, loss of function of TNNT2 has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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