ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.62317C>A (p.Leu20773Met) (rs375173874)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000727330 SCV000236772 likely benign not provided 2020-01-17 criteria provided, single submitter clinical testing
Invitae RCV000531028 SCV000643480 uncertain significance Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2017-12-06 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000727330 SCV000707596 uncertain significance not provided 2017-12-14 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000727330 SCV001152831 likely benign not provided 2017-04-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000184155 SCV001442592 likely benign not specified 2020-10-01 criteria provided, single submitter clinical testing Variant summary: TTN c.54613C>A (p.Leu18205Met) results in a conservative amino acid change located in the A-band domain of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 9.7e-05 in 279510 control chromosomes, predominantly at a frequency of 0.00099 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 3 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.54613C>A in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (2x) and likely benign (2x). Based on the evidence outlined above, the variant was classified as likely benign.

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