ClinVar Miner

Submissions for variant NM_000363.5(TNNI3):c.406C>T (p.Arg136Ter)

dbSNP: rs1393946566
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000578828 SCV000680788 uncertain significance not provided 2022-11-07 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene or region of a gene for which loss of function is not a well-established mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001295096 SCV001484007 uncertain significance Hypertrophic cardiomyopathy 2022-07-31 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 488853). 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. This variant has not been reported in the literature in individuals affected with TNNI3-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Arg136*) in the TNNI3 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in TNNI3 cause disease.
Ambry Genetics RCV002325114 SCV002631992 uncertain significance Cardiovascular phenotype 2021-05-17 criteria provided, single submitter clinical testing The p.R136* variant (also known as c.406C>T), located in coding exon 7 of the TNNI3 gene, results from a C to T substitution at nucleotide position 406. This changes the amino acid from an arginine to a stop codon within coding exon 7. Truncating alterations in TNNI3 have been reported in patients with restrictive cardiomyopathy (RCM) and hypertrophic cardiomyopathy (HCM) (Kaski JP et al. Heart. 2008;94(11):1478-84; Kostareva A et al. Int J Cardiol. 2009;131(3):410-2; Olivotto I et al. J Am Coll Cardiol. 2011;58(8):839-48; van den Wijngaard A et al. Neth Heart J. 2011;19(7-8):344-51). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. However, loss of function of TNNI3 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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