ClinVar Miner

Submissions for variant NM_000364.4(TNNT2):c.436G>A (p.Glu146Lys) (rs371142225)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000646066 SCV000767823 uncertain significance Familial hypertrophic cardiomyopathy 2; Left ventricular noncompaction 6; Familial restrictive cardiomyopathy 3 2018-06-17 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 136 of the TNNT2 protein (p.Glu136Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs371142225, ExAC 0.002%). This variant has been observed in an individual affected with dilated cardiomyopathy (PMID: 28416588). This variant has also been observed in an individual affected with restrictive cardiomyopathy, but also in his father and brother, both unaffected (PMID: 18467357). This variant is also known as p.E131K in the literature. ClinVar contains an entry for this variant (Variation ID: 180552). A computational algorithm designed to assess the pathogenicity of variants in TNNT2 with regard to hypertrophic cardiomyopathy predicted this sequence change to be deleterious. The algorithm has a sensitivity of 94% and a specificity of 89% (PMID: 21310275). 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.
Blueprint Genetics RCV000157536 SCV000207282 uncertain significance Primary dilated cardiomyopathy 2014-09-29 no assertion criteria provided clinical testing

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