ClinVar Miner

Submissions for variant NM_000363.5(TNNI3):c.556C>T (p.Arg186Trp) (rs760978512)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000658349 SCV000780121 uncertain significance not provided 2018-05-29 criteria provided, single submitter clinical testing The R186W variant of uncertain significance in the TNNI3 gene has not been published as pathogenic or been reported as benign to our knowledge. This variant is observed in 4/277,072 alleles from individuals of various ethnic backgrounds in large population cohorts (Lek et al., 2016). The R186W 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. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Furthermore, other pathogenic or likely pathogenic missense variants in nearby residues (E184K, R186Q, V188M, D190Y) have been reported in the Human Gene Mutation Database or at GeneDx in association with cardiomyopathy (Stenson et al., 2014), supporting the functional importance of this region of the protein. However, this variant lacks observation in a significant number of affected individuals, segregation data, and functional evidence, which would further clarify its pathogenicity.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
Color Health, Inc RCV001177934 SCV001342250 uncertain significance Cardiomyopathy 2018-11-11 criteria provided, single submitter clinical testing

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