ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.107576T>C (p.Met35859Thr) (rs72629793)

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Total submissions: 17
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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 RCV000082477 SCV000054858 likely benign not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000040989 SCV000064680 benign not specified 2017-10-12 criteria provided, single submitter clinical testing p.Met33291Thr variant in exon 311 of TTN: This variant is not expected to have c linical significance because it has been identified in 0.9% (275/30782) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomAD.bro adinstitute.org; dbSNP rs72629793). ACMG/AMP Criteria applied: BA1(Richards 2015 ).
GeneDx RCV000040989 SCV000236912 benign not specified 2016-08-16 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 RCV001079456 SCV000286423 benign Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-12-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000241675 SCV000317426 benign Cardiovascular phenotype 2020-05-29 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000040989 SCV000337108 likely benign not specified 2016-08-02 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000082477 SCV000493399 uncertain significance not provided 2018-06-01 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000082477 SCV000844611 benign not provided 2018-03-28 criteria provided, single submitter clinical testing
Mendelics RCV000986935 SCV001136094 benign Dilated cardiomyopathy 1G 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001128833 SCV001288326 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 RCV000986935 SCV001295625 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV001135821 SCV001295626 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). 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 RCV001135822 SCV001295627 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 RCV001135823 SCV001295628 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001171215 SCV001333917 benign Cardiomyopathy 2017-11-28 criteria provided, single submitter clinical testing
Genetics and Genomics Program,Sidra Medicine RCV001293191 SCV001434189 likely benign Primary dilated cardiomyopathy criteria provided, single submitter research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000040989 SCV001623316 benign not specified 2021-04-20 criteria provided, single submitter clinical testing Variant summary: TTN c.99872T>C (p.Met33291Thr) results in a non-conservative amino acid change located in the M-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 0.0019 in 249108 control chromosomes, predominantly at a frequency of 0.0088 within the South Asian subpopulation in the gnomAD database, including 4 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 22.5- 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 a benign polymorphism found primarily in populations of South Asian origin. c.99872T>C has been reported in the literature in individuals affected with Dilated Cardiomyopathy (e.g. Taylor_2011). These reports do 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 other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, citing the variant as benign/likely benign (n=9) and uncertain significance (n=2). Based on the evidence outlined above, the variant was classified as benign.

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