ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.30512-19dup (rs397517532)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000040108 SCV000063799 likely benign not specified 2011-09-27 criteria provided, single submitter clinical testing
GeneDx RCV000040108 SCV000236630 benign not specified 2018-03-15 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.
Illumina Clinical Services Laboratory,Illumina RCV000396427 SCV000423781 likely benign Dilated Cardiomyopathy, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000307434 SCV000423782 likely benign Myopathy, early-onset, with fatal cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000341302 SCV000423783 likely benign Myopathy, myofibrillar, 9, with early respiratory failure 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000396421 SCV000423784 likely benign Tibial muscular dystrophy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000359205 SCV000423786 likely benign Limb-Girdle Muscular Dystrophy, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000423669 SCV000510581 benign not provided 2017-02-16 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000040108 SCV001362650 benign not specified 2019-08-19 criteria provided, single submitter clinical testing Variant summary: TTN c.26780-10dupT 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 0.1 in 201596 control chromosomes in the gnomAD database, including 809 homozygotes. The observed variant frequency is approximately 166 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 benign. To our knowledge, no occurrence of c.26780-10dupT in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (2x) /likely benign (1x). Based on the evidence outlined above, the variant was classified as benign.

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