ClinVar Miner

Submissions for variant NM_000363.5(TNNI3):c.143A>C (p.Gln48Pro)

gnomAD frequency: 0.00002  dbSNP: rs200720341
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000253227 SCV000320623 uncertain significance Cardiovascular phenotype 2022-02-09 criteria provided, single submitter clinical testing The p.Q48P variant (also known as c.143A>C), located in coding exon 4 of the TNNI3 gene, results from an A to C substitution at nucleotide position 143. The glutamine at codon 48 is replaced by proline, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001051959 SCV001216144 uncertain significance Hypertrophic cardiomyopathy 2023-07-16 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 48 of the TNNI3 protein (p.Gln48Pro). This variant is present in population databases (rs200720341, gnomAD 0.02%). 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: 264596). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001798763 SCV002042728 uncertain significance Cardiomyopathy 2019-12-27 criteria provided, single submitter clinical testing
GeneDx RCV002253343 SCV002525440 uncertain significance not provided 2022-03-07 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000656735 SCV000778807 uncertain significance Dilated cardiomyopathy 2A 2018-06-06 no assertion criteria provided clinical testing The observed variant c.143A>C (p.Gln48Pro) is not reported in 1000 Genomes and its minor allele frequency in ExAC databases is 0.0001253. The in silico prediction of the variant is disease causing by MutationTaster2, Tolerated by SIFT and possibly damaging by PolyPhen2.

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