ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.80701A>G (p.Ile26901Val) (rs201562505)

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Total submissions: 20
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000152207 SCV000200968 likely benign not specified 2019-05-10 criteria provided, single submitter clinical testing The p.Ile24333Val variant in TTN is classified as likely benign because it has been identified in 3.1% (326/10344) of Ashkenazi Jewish chromosomes (including 1 homozygote) and 0.04% (59/127920) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). Additionally, isoleucine (Ile) at position 24333 is not conserved in evolution and multiple birds and reptiles carry a valine (Val) at this position. Computational prediction tools predict that this variant does not impact the protein. ACMG/AMP Criteria applied: BS1, BP4.
GeneDx RCV000152207 SCV000237602 benign not specified 2017-07-24 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.
Genetic Services Laboratory, University of Chicago RCV000152207 SCV000249281 uncertain significance not specified 2014-10-31 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000152207 SCV000257869 uncertain significance not specified 2015-07-10 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000152207 SCV000332584 benign not specified 2017-06-22 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000369763 SCV000421519 uncertain significance Myopathy, early-onset, with fatal cardiomyopathy 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000273789 SCV000421520 benign Tibial muscular dystrophy 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000364915 SCV000421522 uncertain significance Limb-girdle muscular dystrophy, type 2J 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000270152 SCV000421523 benign Myopathy, myofibrillar, 9, with early respiratory failure 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000325455 SCV000421524 uncertain significance Dilated cardiomyopathy 1G 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV000471832 SCV000555253 likely benign Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-12-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV000617421 SCV000735451 benign Cardiovascular phenotype 2017-12-08 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
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769931 SCV000901357 likely benign Cardiomyopathy 2017-08-09 criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852807 SCV000995535 benign Primary dilated cardiomyopathy 2018-04-06 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000152207 SCV001448542 benign not specified 2020-11-17 criteria provided, single submitter clinical testing Variant summary: TTN c.72997A>G (p.Ile24333Val) results in a conservative amino acid change located in the A-band region (cardiodb.org) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0016 in 248414 control chromosomes in the gnomAD database, including 1 homozygote. The observed variant frequency is approximately 4.2- 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.72997A>G has been reported in the literature in individuals affected with Cardiomyopathy (e.g. Pugh_2014, Campuzano_2015, Restrepo-Cordoba_2017). 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. Ten other ClinVar submitters (evaluation after 2014) have cited the variant as benign/likely benign (n=8) and uncertain significance (n=2). Based on the evidence outlined above, the variant was classified as benign.
Athena Diagnostics Inc RCV000152207 SCV001879707 benign not specified 2020-12-01 criteria provided, single submitter clinical testing
GenomeConnect, ClinGen RCV001249283 SCV001423231 not provided TTN-Related Disorders no assertion provided phenotyping only Variant interpretted as Uncertain significance and reported on 07-09-2015 by Lab or GTR ID 500060. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV001530137 SCV001744833 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000152207 SCV001919823 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV001530137 SCV001953202 likely benign not provided no assertion criteria provided clinical testing

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