ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.59318A>G (p.Glu19773Gly) (rs371719028)

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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 RCV000172655 SCV000054973 likely benign not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000040419 SCV000064110 uncertain significance not specified 2014-06-18 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Glu17205Gly var iant in TTN has been identified by our laboratory in 1 African American individu al with DCM and possible LVNC. This variant has also been identified in 0.2% (9/ 3840) of African American chromosomes by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS/; dbSNP rs371719028). Computational prediction too ls and conservation analysis do not provide strong support for or against an imp act to the protein. In summary, while the clinical significance of the Glu17205G ly variant is uncertain, its frequency suggests that it is more likely to be ben ign.
GeneDx RCV000040419 SCV000237354 likely benign not specified 2017-12-19 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000172655 SCV000333438 uncertain significance not provided 2015-07-31 criteria provided, single submitter clinical testing
Invitae RCV001085920 SCV000555377 likely benign Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-12-06 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000172655 SCV001152845 uncertain significance not provided 2019-04-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000040419 SCV001437319 benign not specified 2020-09-25 criteria provided, single submitter clinical testing Variant summary: TTN c.51614A>G (p.Glu17205Gly) results in a non-conservative amino acid change located in the A-band region of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00022 in 279750 control chromosomes, predominantly at a frequency of 0.0026 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 6.5-fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Dilated Cardiomyopathy phenotype (0.00039), 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.51614A>G in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as likely benign (2x), or VUS (2x). Based on the evidence outlined above, the variant was classified as benign.

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