ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.20341G>A (p.Glu6781Lys) (rs72648958)

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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 RCV000172694 SCV000051449 likely benign not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000039941 SCV000063632 uncertain significance not specified 2014-09-19 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Glu5537Lys va riant in TTN has been identified by our laboratory in 1 Caucasian adult with HCM who also carried a likely disease-causing variant in another gene, 1 adult of u nspecified ethnicity with DCM, and 1 African American infant with severe RVH. Th is variant has also been identified in 0.1% (12/8216) of European American chrom osomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/, Ng 2013; dbSNP rs72648958). Computational prediction tools and conservation ana lysis do not provide strong support for or against an impact to the protein. In summary, while the clinical significance of the p.Glu5537Lys variant is uncertai n, its presence in various cardiomyopathies with different mechanisms of disease and its frequency in controls suggests that it is more likely to be benign.
GeneDx RCV000039941 SCV000238282 likely benign not specified 2017-11-27 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 RCV001079880 SCV000286491 likely benign Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-12-08 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000172694 SCV000333068 uncertain significance not provided 2018-08-30 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000039941 SCV000597705 uncertain significance not specified 2016-09-20 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000039941 SCV000616018 benign not specified 2020-08-03 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000172694 SCV001153057 uncertain significance not provided 2020-10-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001131917 SCV001291561 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 RCV001131918 SCV001291562 uncertain significance 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 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 RCV001131919 SCV001291563 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 RCV001132883 SCV001292562 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.
Illumina Clinical Services Laboratory,Illumina RCV001132884 SCV001292563 uncertain significance 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 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000039941 SCV001337973 likely benign not specified 2021-04-26 criteria provided, single submitter clinical testing Variant summary: TTN c.16609G>A (p.Glu5537Lys) results in a conservative amino acid change located in the I-Band region of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.001 in 245308 control chromosomes, predominantly at a frequency of 0.0017 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 3 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 a benign polymorphism found primarily in populations of Non-Finnish European origin. c.16609G>A has been reported in the literature in individuals affected with Cardiomyopathy (Campuzano_2015, Mademont-Soler_2017, Mates_2018). 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. Nine ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=5), likely benign (n=2) and benign (n=2). Based on the evidence outlined above, the variant was classified as likely benign.
Baylor Genetics RCV001132883 SCV001528488 uncertain significance Myopathy, myofibrillar, 9, with early respiratory failure 2018-01-18 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Mayo Clinic Laboratories, Mayo Clinic RCV000172694 SCV001713251 uncertain significance not provided 2020-06-25 criteria provided, single submitter clinical testing

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