ClinVar Miner

Submissions for variant NM_000363.5(TNNI3):c.109-17C>A (rs139150276)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000168945 SCV000169012 benign not specified 2012-04-16 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000168945 SCV001361443 benign not specified 2019-11-04 criteria provided, single submitter clinical testing Variant summary: TNNI3 c.109-17C>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.004 in 170270 control chromosomes, predominantly at a frequency of 0.051 within the East Asian subpopulation in the gnomAD database, including 20 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 408 fold of the estimated maximal expected allele frequency for a pathogenic variant in TNNI3 causing Hypertrophic Cardiomyopathy phenotype (0.00013), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.109-17C>A has been reported in the literature in individuals affected with Hypertrophic Cardiomyopathy (Kimura_1997). The report does not provide unequivocal conclusions about association of the variant with Hypertrophic Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV001529157 SCV001742157 likely benign not provided no assertion criteria provided clinical testing

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