ClinVar Miner

Submissions for variant NM_000364.4(TNNT2):c.854G>A (p.Arg285His) (rs397516484)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Agnes Ginges Centre for Molecular Cardiology,Centenary Institute RCV000201870 SCV000256639 uncertain significance Familial hypertrophic cardiomyopathy 1 2015-02-11 criteria provided, single submitter research This TNNT2 Arg278His variant has been reported in one HCM family and was absent in 200 normal control individuals (Pasquale F, et al., 2012). This variant is rare and is present at low frequencies in the 1000 genomes project (MAF=0.0002; http://www.1000genomes.org/), and the Exome Aggregation Consortium dataset (MAF=0.00002; http://exac.broadinstitute.org/). We have identified TNNT2 Arg278His in 1 HCM proband who has no family history of disease or SCD. Interestingly, different rare variants at this position (Arg278Cys and Arg278Pro) have also been reported in multiple HCM individuals, suggesting that an amino acid substitution at this site may not be tolerated. Computational tools SIFT, MutationTaster, and PolyPhen-2 predict this variant to have a deleterious effect, but no prediction is called by PolyPhen-HCM. In summary, based on the current literature and our limited familial data, we classify TNNT2 Arg278His as a variant of "uncertain significance". Further evidence is required to fully understand its pathogenic role in HCM.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000036623 SCV000060278 uncertain significance not specified 2008-03-01 no assertion criteria provided clinical testing

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