ClinVar Miner

Submissions for variant NM_001276345.2(TNNT2):c.644G>A (p.Arg215Gln)

dbSNP: rs121964860
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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 RCV000152098 SCV000200753 uncertain significance not specified 2013-06-13 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The Arg205Gln v ariant in TNNT2 has not been reported in individuals with cardiomyopathy or in l arge population studies. Computational analyses (biochemical amino acid properti es, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Two other variants at this position (Ar g205Leu and Arg205Trp) have been reported in individuals with DCM and the Arg205 Leu variant segregated in two affected relatives (Mogensen 2004, Hershberger 200 9). Functional studies for these 2 variants also suggest an impact to the protei n, though it is unknown if these in vitro assays accurately represent biological function (Mogensen 2004, Hershberger 2009). In summary, the identification of o ther variants at this position in individuals with DCM suggests that change at t his position may not be tolerated, but additional studies are needed to fully as sess the clinical significance of this variant.
Invitae RCV000464711 SCV000541931 pathogenic Hypertrophic cardiomyopathy 2; Dilated cardiomyopathy 1D; Cardiomyopathy, familial restrictive, 3 2021-08-31 criteria provided, single submitter clinical testing
GeneDx RCV000786227 SCV001777959 pathogenic not provided 2021-10-07 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies demonstrate R205Q mutant thin filaments exhibited decreased Ca 2+ sensitivity (Pan et al., 2015); Reported in ClinVar but additional evidence is not available (ClinVar Variant ID 165539; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 20031601, 15542288, 15923195, 23897817, 22675533, 26498512)
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000786227 SCV000924965 likely pathogenic not provided 2016-08-03 no assertion criteria provided provider interpretation

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