ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.102657T>A (p.Ser34219Arg)

gnomAD frequency: 0.00038  dbSNP: rs370077023
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000725232 SCV000237903 likely benign not provided 2021-06-04 criteria provided, single submitter clinical testing
Eurofins NTD LLC (GA) RCV000725232 SCV000335185 uncertain significance not provided 2018-09-11 criteria provided, single submitter clinical testing
Invitae RCV000544778 SCV000642524 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-11-06 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001844076 SCV002104070 likely benign not specified 2022-02-07 criteria provided, single submitter clinical testing Variant summary: TTN c.94953T>A (p.Ser31651Arg) results in a non-conservative amino acid change located in the M-band region of the encoded protein sequence. Four 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 248982 control chromosomes, predominantly at a frequency of 0.0017 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 4 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.94953T>A in individuals affected with Dilated Cardiomyopathy/Limb Girdle Muscular Dystrophy or other TTN-related disorders and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (Likely Benign, n=2; VUS, n=2). Based on the evidence outlined above, the variant was classified as likely benign.

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