ClinVar Miner

Submissions for variant NM_015978.3(TNNI3K):c.681T>C (p.Asp227=)

gnomAD frequency: 0.00004  dbSNP: rs757108060
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001972062 SCV002208715 uncertain significance not provided 2025-01-12 criteria provided, single submitter clinical testing This sequence change affects codon 227 of the TNNI3K mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the TNNI3K protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs757108060, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with TNNI3K-related conditions. ClinVar contains an entry for this variant (Variation ID: 1431414). 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.
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV002471191 SCV002766833 uncertain significance Atrial conduction disease 2022-03-31 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3C. Following criteria are met: 0101 - Gain of function is a known mechanism of disease in this gene and is associated with cardiac conduction disease with or without dilated cardiomyopathy (MIM#616117). Loss of function and dominant negative have also been suggested as mechanisms, but current evidence is limited (PMIDs: 30010057, 34203974). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0218 - Non-coding variant without known or predicted effect. This variant is predicted to result in a synonymous change. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v2 & v3) <0.001 for a dominant condition (11 heterozygotes, 0 homozygotes). (SP) 0506 - Abnormal splicing is not predicted and nucleotide is poorly conserved. (SB) 0705 - No comparable variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Genome-Nilou Lab RCV002471191 SCV004049416 uncertain significance Atrial conduction disease 2023-04-11 criteria provided, single submitter clinical testing

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