ClinVar Miner

Submissions for variant NM_000363.5(TNNI3):c.544G>A (p.Glu182Lys)

dbSNP: rs397516355
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Mass General Brigham Personalized Medicine RCV000036303 SCV000059955 pathogenic Primary dilated cardiomyopathy 2014-09-10 criteria provided, single submitter clinical testing The Glu182Lys variant in TNNI3 has been identified by our laboratory as de novo in 1 African American neonate with DCM and 1 Caucasian infant with DCM. In addit ion, it has not been identified in large population studies. Computational predi ction tools and conservation analysis do not provide strong support for or again st an impact to the protein. In summary, this variant meets our criteria to be c lassified as pathogenic ( based upon de novo occurrence in multiple cases.
GeneDx RCV000159235 SCV000209181 pathogenic not provided 2012-10-25 criteria provided, single submitter clinical testing The Glu182Lys mutation in the TNNI3 gene has been reported in association with cardiomyopathy (Lakdawala N et al., 2012). Lakdawla et al. reported Glu182Lys occurred de novo in one patient with DCM and it was absent from approximately 400 control samples. Also, the NHLBI ESP Exome Variant Server reports Glu182Lys was not observed in approximately 6,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. Glu182Lys results in a non-conservative amino acid substitution of a negatively charged Glutamic acid with a positively charged Lysine at a position that is highly conserved across species. Furthermore, mutations in nearby codons (Lys183Asn, Lys183Glu, Asn185Lys, Arg186Gln) have been reported in association with cardiomyopathy, supporting the functional importance of this region of the protein. In summary, Glu182Lys in the TNNI3 gene is interpreted as a disease-causing mutation. The variant is found in DCM panel(s).
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001170613 SCV001333202 likely pathogenic Cardiomyopathy 2018-12-12 criteria provided, single submitter clinical testing
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000036303 SCV000804930 likely pathogenic Primary dilated cardiomyopathy 2015-10-12 no assertion criteria provided clinical testing

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