Submissions for variant NM_000363.5(TNNI3):c.233C>T (p.Thr78Ile)

gnomAD frequency: 0.00001  dbSNP: rs786205288

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000222876	SCV000272522	uncertain significance	not specified	2015-11-09	criteria provided, single submitter	clinical testing	The p.Thr78Ile variant in TNNI3 has not been previously reported in individuals with cardiomyopathy. Data from large population studies is insufficient to asses s the frequency of this variant. Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Thr78Ile variant is uncertain.
Color Diagnostics, LLC DBA Color Health	RCV003532060	SCV004359910	uncertain significance	Cardiomyopathy	2023-03-28	criteria provided, single submitter	clinical testing	This missense variant replaces threonine with isoleucine at codon 78 of the TNNI3 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TNNI3-related disorders in the literature. This variant has been identified in 2/240612 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.