ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.3409G>C (p.Gly1137Arg) (rs72647870)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000172731 SCV000051508 likely benign not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000040219 SCV000063910 likely benign not specified 2014-12-30 criteria provided, single submitter clinical testing p.Gly1137Arg in exon 21 of TTN: This variant is not expected to have clinical si gnificance because it has been identified in 0.3% (230/67514) of European chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs72647870).
GeneDx RCV000040219 SCV000237842 benign not specified 2017-01-13 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.
Invitae RCV001084204 SCV000286592 likely benign Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-11-21 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000040219 SCV000315484 likely benign not specified criteria provided, single submitter clinical testing
Ambry Genetics RCV000250640 SCV000318003 likely benign Cardiovascular phenotype 2019-02-07 criteria provided, single submitter clinical testing Other strong data supporting benign classification
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000040219 SCV000332048 likely benign not specified 2015-06-11 criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852941 SCV000995687 likely benign Hypertrophic cardiomyopathy 2017-07-06 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000172731 SCV001153189 uncertain significance not provided 2019-02-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001129652 SCV001289192 uncertain significance Myopathy, early-onset, with fatal cardiomyopathy 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001129653 SCV001289193 benign Limb-girdle muscular dystrophy, type 2J 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV001129654 SCV001289194 benign Tibial muscular dystrophy 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV001129655 SCV001289195 likely benign Dilated cardiomyopathy 1G 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV001132367 SCV001292026 benign Myopathy, myofibrillar, 9, with early respiratory failure 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000040219 SCV001337971 likely benign not specified 2020-01-20 criteria provided, single submitter clinical testing Variant summary: TTN c.3409G>C (p.Gly1137Arg) results in a non-conservative amino acid change located near the Z-disk region of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0022 in 251114 control chromosomes. The observed variant frequency is approximately 3.45 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.3409G>C in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (n=1)/likely benign (n=3). Based on the evidence outlined above, the variant was classified as likely benign.

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