ClinVar Miner

Submissions for variant NM_000363.5(TNNI3):c.108+4G>T

gnomAD frequency: 0.00001  dbSNP: rs878853954
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000229820 SCV000284650 uncertain significance Hypertrophic cardiomyopathy 2022-04-24 criteria provided, single submitter clinical testing This sequence change falls in intron 3 of the TNNI3 gene. It does not directly change the encoded amino acid sequence of the TNNI3 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TNNI3-related conditions. ClinVar contains an entry for this variant (Variation ID: 237688). Variants that disrupt 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 is not likely to affect RNA splicing. 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.
New York Genome Center RCV003448291 SCV004176217 uncertain significance Cardiomyopathy, familial restrictive, 1; Dilated cardiomyopathy 1FF; Hypertrophic cardiomyopathy 7 2023-08-09 criteria provided, single submitter clinical testing The c.108+4G>T variant in the TNNI3 gene has not previously been reported in the literature and it has been deposited in ClinVar [ClinVar ID: 237688] as a Variant of Uncertain Significance (1 submission). The c.108+4G>T variant is observed as a single heterozygous allele in population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze 8), suggesting it is not a common benign variant in the populations represented in those databases. The c.108+4G>T variant is located in intron 3 (of 7) of the TNNI3 gene and is predicted to have no significant effect on canonical mRNA splicing [Splice AI = 0.00]. However, there are no functional studies to support or refute all these in silico splicing predictions. Based on available evidence this c.108+4G>T variant identified in TNNI3 is classified as a Variant of Uncertain Significance.

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