ClinVar Miner

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

gnomAD frequency: 0.00238  dbSNP: rs200350579
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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham 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, http://exac.broadinstitute.org) .
Eurofins Ntd Llc (ga) RCV000040706 SCV000114461 benign not specified 2013-05-29 criteria provided, single submitter clinical testing
GeneDx RCV001703909 SCV000237653 likely benign not provided 2021-03-02 criteria provided, single submitter clinical testing
Invitae RCV000226402 SCV000286873 benign Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2024-01-29 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 benign Cardiomyopathy 2023-01-09 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.
Genome-Nilou Lab RCV001839709 SCV002102316 benign Autosomal recessive limb-girdle muscular dystrophy type 2J 2021-09-10 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001839710 SCV002102318 benign Myopathy, myofibrillar, 9, with early respiratory failure 2021-09-10 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001839711 SCV002102319 benign Early-onset myopathy with fatal cardiomyopathy 2021-09-10 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001839708 SCV002102320 benign Tibial muscular dystrophy 2021-09-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV002345325 SCV002649650 benign Cardiovascular phenotype 2018-10-30 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Clinical Genetics, Academic Medical Center RCV000040706 SCV001918431 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000040706 SCV001966698 benign not specified no assertion criteria provided clinical testing

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