ClinVar Miner

Submissions for variant NM_000363.5(TNNI3):c.88G>A (p.Ala30Thr) (rs796104366)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000246508 SCV000319760 uncertain significance Cardiovascular phenotype 2018-01-18 criteria provided, single submitter clinical testing The p.A30T variant (also known as c.88G>A), located in coding exon 3 of the TNNI3 gene, results from a G to A substitution at nucleotide position 88. The alanine at codon 30 is replaced by threonine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV000493547 SCV000583326 uncertain significance not provided 2017-05-19 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the TNNI3 gene. The A30T variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A30T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position where amino acids with similar properties to alanine are tolerated across species and where threonine is present as the wild type in at least one species. Finally, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Invitae RCV000814858 SCV000955290 uncertain significance Hypertrophic cardiomyopathy 2019-10-02 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 30 of the TNNI3 protein (p.Ala30Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TNNI3-related disease. ClinVar contains an entry for this variant (Variation ID: 264087). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). 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.
Color Health, Inc RCV001183000 SCV001348645 uncertain significance Cardiomyopathy 2019-12-02 criteria provided, single submitter clinical testing

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