ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.9488G>A (p.Arg3163His) (rs149755500)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000172724 SCV000051337 likely benign not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000152483 SCV000201615 uncertain significance not specified 2015-05-26 criteria provided, single submitter clinical testing The p.Arg3163His variant in TTN has been previously identified by our laboratory in 1 unaffected individual with a family history of DCM, hypertrophy with fibro sis, and SCD. It has also been identified in 19/66478 European chromosomes by th e Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs14 9755500). Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive e nough to determine pathogenicity. In summary, the clinical significance of the p.Arg3163His variant is uncertain.
GeneDx RCV000172724 SCV000238062 uncertain significance not provided 2017-10-12 criteria provided, single submitter clinical testing The R3163H variant has been observed in an individual with coronary artery disease; however no additional clinical information was provided and the authors thought this variant was likely not pathogenic (Ng et al., 2013). The R3163H variant is observed in 45/125882 (.036%) alleles from individuals of European Non-Finnish background. The R3163H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, the R3163H variant is not located in the A-band nor the M-line region of titin, where the majority of pathogenic truncating variants have been reported. However, this substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.TTN-related disorders can be inherited in an autosomal dominant or autosomal recessive manner.
Invitae RCV000460977 SCV000542703 uncertain significance Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2016-09-15 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000172724 SCV000701245 uncertain significance not provided 2017-01-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV000617183 SCV000735600 likely benign Cardiovascular phenotype 2019-08-19 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001171057 SCV001333726 likely benign Cardiomyopathy 2019-04-01 criteria provided, single submitter clinical testing

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