ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.10115-4G>A (rs367648529)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001083169 SCV000286388 likely benign Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-11-25 criteria provided, single submitter clinical testing
Phosphorus, Inc. RCV000577970 SCV000679938 uncertain significance Dilated cardiomyopathy 1G 2017-08-01 criteria provided, single submitter clinical testing
Phosphorus, Inc. RCV000578025 SCV000679939 uncertain significance Limb-girdle muscular dystrophy, type 2J 2017-08-01 criteria provided, single submitter clinical testing
Phosphorus, Inc. RCV000578101 SCV000679940 uncertain significance Tibial muscular dystrophy 2017-08-01 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000726929 SCV000704209 uncertain significance not provided 2016-12-07 criteria provided, single submitter clinical testing
GeneDx RCV000726929 SCV000730986 likely benign not provided 2021-03-18 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 23396983)
Ambry Genetics RCV000619673 SCV000737244 likely benign Cardiovascular phenotype 2020-02-06 criteria provided, single submitter clinical testing In silico models in agreement (benign);Insufficient evidence
CeGaT Praxis fuer Humangenetik Tuebingen RCV000726929 SCV001153159 uncertain significance not provided 2018-07-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000591543 SCV001363829 uncertain significance not specified 2019-09-16 criteria provided, single submitter clinical testing Variant summary: TTN c.10115-4G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0001 in 249358 control chromosomes, predominantly at a frequency of 0.00013 within the Non-Finnish European subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in TTN causing Cardiomyopathy (0.0001 vs 0.00063), allowing no conclusion about variant significance. c.10115-4G>A has been reported in the literature in individuals affected with Cardiomyopathy and sudden unexplained death (SUD)(Campuzano_2015, Lopes_2013). These reports do 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. Five ClinVar submissions (evaluation after 2014) cite the variant three times as uncertain significance and twice as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000726929 SCV001743263 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000591543 SCV001919360 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000726929 SCV001959616 likely benign not provided no assertion criteria provided clinical testing

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