ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.84461C>T (p.Pro28154Leu) (rs200350579)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000040706 SCV000064397 likely benign not specified 2015-06-25 criteria provided, single submitter clinical testing p.Pro25586Leu in exon 275 of TTN: This variant is not expected to have clinical significance because it has been identified in 0.85% (83/9754) of African chromo somes by the Exome Aggregation Consortium (ExAC, .
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000040706 SCV000114461 benign not specified 2013-05-29 criteria provided, single submitter clinical testing
GeneDx RCV000040706 SCV000237653 likely benign not specified 2017-12-26 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000226402 SCV000286873 benign Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-11-21 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000040706 SCV000616157 benign not specified 2017-01-24 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769918 SCV000901344 likely benign Cardiomyopathy 2015-10-23 criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852802 SCV000995529 likely benign Heart failure 2018-07-03 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000040706 SCV001370715 likely benign not specified 2020-05-11 criteria provided, single submitter clinical testing Variant summary: TTN c.76757C>T (p.Pro25586Leu) results in a non-conservative amino acid change located in the A-band domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00073 in 274494 control chromosomes, predominantly at a frequency of 0.0082 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 13 fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Cardiomyopathy phenotype (0.00063), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.76757C>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Six ClinVar submitters (evaluation after 2014) cite the variant as benign (2x) and likely benign (4x). Based on the evidence outlined above, the variant was classified as likely benign.

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