ClinVar Miner

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

gnomAD frequency: 0.00293  dbSNP: rs72647870
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Total submissions: 16
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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,Mass General Brigham 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; Autosomal recessive limb-girdle muscular dystrophy type 2J 2021-12-17 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
Eurofins NTD LLC (GA) 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 Center for Human Genetics Tuebingen RCV000172731 SCV001153189 likely benign not provided 2022-05-01 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV001129652 SCV001289192 uncertain significance Early-onset myopathy 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 Laboratory Services,Illumina RCV001129653 SCV001289193 benign Autosomal recessive 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 Laboratory Services,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 Laboratory Services,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 Laboratory Services,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 benign not specified 2021-08-05 criteria provided, single submitter clinical testing Variant summary: TTN c.3409G>C (p.Gly1137Arg) results in a non-conservative amino acid change located in the near 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 395852 control chromosomes in the gnomAD database (v2.1 and v3.1 datasets), including 1 homozygote. The observed variant frequency is approximately 5.75 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 benign. c.3409G>C has been reported in the literature in individuals affected with individuals affected with hypertrophic cardiomyopathy and sudden unexplained death, however in at least one of these patients co-occurring potentially pathogenic variant(s) could explain the phenotype (Lopes_2013, Campuzano_2015). These reports do not support the association of the variant with Dilated Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight other submitters have provided clinical-significance assessments for this variant in ClinVar after 2014 without evidence for independent evaluation, and classified the variant as VUS (1x), likely benign (6x) / benign (1x). Based on the evidence outlined above, the variant was classified as benign.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001798150 SCV002042455 benign Cardiomyopathy 2019-08-30 criteria provided, single submitter clinical testing

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