ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.97760G>A (p.Arg32587His) (rs55704830)

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Total submissions: 19
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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 RCV000154034 SCV000051469 likely benign not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000040857 SCV000064548 likely benign not specified 2015-09-14 criteria provided, single submitter clinical testing p.Arg30019His in exon 299 of TTN: This variant is not expected to have clinical significance because it has been identified in 0.5% (61/10980) of European chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org ; dbSNP rs55704830).
GeneDx RCV000154034 SCV000237840 benign not provided 2020-06-03 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 18948003, 1745277, 12669942, 23861362, 24105469, 24395473, 21810661, 22335739, 23418287, 23518707, 21617319, 10462489, 11717165, 12145747, 17444505)
Invitae RCV001080383 SCV000286947 benign Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-12-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV000250297 SCV000318653 uncertain significance Inborn genetic diseases 2014-06-05 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000040857 SCV000333098 likely benign not specified 2015-07-30 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000343661 SCV000420511 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 RCV000401798 SCV000420512 uncertain significance Limb-girdle muscular dystrophy, type 2J 2017-07-25 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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV000295583 SCV000420513 benign Myopathy, myofibrillar, 9, with early respiratory failure 2017-07-25 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 RCV000407558 SCV000420515 uncertain significance Dilated cardiomyopathy 1G 2017-07-25 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 RCV000313220 SCV000420516 benign Tibial muscular dystrophy 2017-07-25 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.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000154034 SCV000610530 likely benign not provided 2017-06-15 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000154034 SCV000892595 uncertain significance not provided 2019-10-01 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769864 SCV000901290 benign Cardiomyopathy 2019-03-29 criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000769864 SCV000995508 likely benign Cardiomyopathy 2017-12-06 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000040857 SCV001442619 likely benign not specified 2020-10-08 criteria provided, single submitter clinical testing Variant summary: TTN c.90056G>A (p.Arg30019His) results in a non-conservative amino acid change located in the A- band region (cardiodb.org) 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 0.0017 in 167792 control chromosomes. The observed variant frequency is approximately 4.4- fold 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.90056G>A has been reported in the literature in at least one individual affected with Dilated Cardiomyopathy without strong evidence for causality (e.g. Headrick_2018). This report does not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 11 clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (uncetain significance, n=3; benign/likely benign, n=8). Based on the evidence outlined above, the variant was classified as likely benign.
New York Genome Center RCV001281439 SCV001468747 uncertain significance Brugada syndrome 2019-07-12 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001287459 SCV001474151 uncertain significance none provided 2020-05-05 criteria provided, single submitter clinical testing The TTN c.97760G>A; p.Arg32587His variant (rs55704830; ClinVar Variation ID: 47588) is rare in the general population (<1% allele frequency in the Genome Aggregation Database) and has not been reported in the medical literature in association with dilated cardiomyopathy (DCM) or other TTN-related disease. The clinical relevance of rare missense variants in this gene, which are identified on average once per individual sequenced in affected populations (Herman 2012), is not well understood. Yet, evidence suggests that the vast majority of such missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Thus, the clinical significance of the p.Arg32587His variant cannot be determined with certainty. References: Begay RL et al. Role of Titin Missense Variants in Dilated Cardiomyopathy. J Am Heart Assoc. 2015 Nov 13;4(11). Herman DS et al. Truncations of titin causing dilated cardiomyopathy. N Engl J Med. 2012 Feb 16;366(7):619-28. Linke and Hamdani. Gigantic business: titin properties and function through thick and thin. Circ Res 2014; 114(6): 1052-1068.
Athena Diagnostics Inc RCV000040857 SCV001879727 benign not specified 2021-03-19 criteria provided, single submitter clinical testing

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