ClinVar Miner

Submissions for variant NM_000363.5(TNNI3):c.114dup (p.Ser39fs)

dbSNP: rs772607683
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484567 SCV000567501 uncertain significance not provided 2021-01-29 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 419596; Landrum et al., 2016); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is not a well-established mechanism of disease; The majority of reported TNNI3 variants in HGMD are missense variants (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 24510615)
Color Diagnostics, LLC DBA Color Health RCV001184324 SCV001350276 uncertain significance Cardiomyopathy 2023-02-16 criteria provided, single submitter clinical testing This variant inserts 1 nucleotide in exon 4 of the TNNI3 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 33495596) and in an individual affected with dilated cardiomyopathy (PMID: 30993396). This variant has also been reported in four ostensibly healthy individuals (PMID: 24510615). This variant has been identified in 2/176158 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Clinical relevance of loss-of-function truncation and splice variants in the TNNI3 gene is not clearly established. The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001865440 SCV002283666 uncertain significance Hypertrophic cardiomyopathy 2023-05-25 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 419596). This variant has not been reported in the literature in individuals affected with TNNI3-related conditions. This variant is present in population databases (rs772607683, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Ser39Ilefs*2) 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.
Fulgent Genetics, Fulgent Genetics RCV002489148 SCV002788825 uncertain significance Dilated cardiomyopathy 2A; Cardiomyopathy, familial restrictive, 1; Dilated cardiomyopathy 1FF; Hypertrophic cardiomyopathy 7 2021-10-20 criteria provided, single submitter clinical testing

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