ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.52022G>A (p.Arg17341Gln) (rs370390570)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000724526 SCV000227983 uncertain significance not provided 2017-09-19 criteria provided, single submitter clinical testing
Invitae RCV001086903 SCV000555474 likely benign Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-10-26 criteria provided, single submitter clinical testing
GeneDx RCV000176344 SCV000732861 likely benign not specified 2017-04-17 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000176344 SCV001363941 likely benign not specified 2019-12-10 criteria provided, single submitter clinical testing Variant summary: TTN c.44318G>A (p.Arg14773Gln) results in a conservative amino acid change located in the A-Band 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 0.00012 in 231806 control chromosomes, predominantly at a frequency of 0.00085 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 1.36 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. c.44318G>A has been reported in the literature in an individual affected with Sudden Arrhythmic Death Syndrome (SADS)(Nunn_2016). This report does not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submissions (evaluation after 2014) cites the variant twice as likely benign and once as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.

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