ClinVar Miner

Submissions for variant NM_000363.5(TNNI3):c.150G>A (p.Lys50=) (rs730881086)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159257 SCV000209203 uncertain significance not provided 2016-12-07 criteria provided, single submitter clinical testing The c.150 G>A variant in the TNNI3 gene has not been reported previously as a pathogenic variant nor as a benign polymorphism, to our knowledge.The G>A substitution alters the last base of exon 4, immediately 5' of the canonical ?GT? of the splice donor site. Moreover, three different splice site prediction algorithms concur that the c.150 G>A variant significantly reduces the efficiency of the normal splice donor site, which is expected to cause abnormal gene splicing.This variant is predicted to lead to either an abnormal message, which is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. In addition, the NHLBI ESP Exome Variant Server reports c.150 G>A was not observed in approximately 2,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. Given the available evidence, we interpret c.150 G>A as a variant of uncertain significance.
Color Health, Inc RCV001186290 SCV001352671 uncertain significance Cardiomyopathy 2018-12-14 criteria provided, single submitter clinical testing
Invitae RCV001342061 SCV001535963 uncertain significance Hypertrophic cardiomyopathy 2020-07-08 criteria provided, single submitter clinical testing This sequence change affects codon 50 of the TNNI3 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the TNNI3 protein. This variant also falls at the last nucleotide of exon 4 of the TNNI3 coding sequence, which is part of the consensus splice site for this exon. This variant is present in population databases (rs730881086, ExAC 0.009%). This variant has been observed in individual(s) with acute myocarditis (PMID: 28359509). ClinVar contains an entry for this variant (Variation ID: 181598). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 28359509). 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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