ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.101212C>T (p.Arg33738Cys)

gnomAD frequency: 0.00613  dbSNP: rs56273463
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 25
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000040902 SCV000064593 likely benign not specified 2015-03-24 criteria provided, single submitter clinical testing p.Arg31170Cys in exon 307 of TTN: This variant is not expected to have clinical significance because it has been identified in 0.8% (522/66702) of European chro mosomes, including 2 homozygotes, by the Exome Aggregation Consortium (ExAC, htt p://exac.broadinstitute.org; dbSNP rs56273463).
Genetic Services Laboratory, University of Chicago RCV000118798 SCV000153421 likely benign not provided 2015-02-10 criteria provided, single submitter clinical testing
GeneDx RCV000118798 SCV000169458 benign not provided 2018-08-22 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 32403337)
PreventionGenetics, part of Exact Sciences RCV000040902 SCV000315623 benign not specified criteria provided, single submitter clinical testing
Ambry Genetics RCV000251517 SCV000318058 likely benign Cardiovascular phenotype 2012-12-10 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Eurofins Ntd Llc (ga) RCV000040902 SCV000332438 benign not specified 2015-07-24 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000334610 SCV000420242 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2J 2018-01-12 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 Laboratory Services, Illumina RCV000407040 SCV000420243 benign Myopathy, myofibrillar, 9, with early respiratory failure 2018-01-12 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 Laboratory Services, Illumina RCV000299708 SCV000420244 likely benign Early-onset myopathy with fatal cardiomyopathy 2018-01-12 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina RCV000349947 SCV000420245 likely benign Dilated cardiomyopathy 1G 2018-01-12 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina RCV000404458 SCV000420246 benign Tibial muscular dystrophy 2018-01-12 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.
Invitae RCV001083282 SCV000555573 benign Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2024-02-01 criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego RCV000852781 SCV000995504 likely benign Atrial fibrillation; Cardiomyopathy 2019-06-11 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000118798 SCV001152602 likely benign not provided 2024-04-01 criteria provided, single submitter clinical testing TTN: BS2
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001170520 SCV001333103 benign Cardiomyopathy 2017-11-09 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000040902 SCV001360681 benign not specified 2019-11-06 criteria provided, single submitter clinical testing Variant summary: TTN c.93508C>T (p.Arg31170Cys) results in a non-conservative amino acid change located in the M-band region of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0056 in 248932 control chromosomes, predominantly at a frequency of 0.0087 within the Non-Finnish European subpopulation in the gnomAD database, including 6 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 14 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. The variant, c.93508C>T, has been reported in the literature in individuals affected with Cardiomyopathy and other cardiac disease phenotypes that are not considered to be associated with the titin related disease spectrum (Pugh_2014, Campuzano_2015). These reports therefore do support the association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six ClinVar submitters (evaluation after 2014) cite the variant as benign (2x), likely benign (3x) and uncertain significance (1x). Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000118798 SCV001471926 likely benign not provided 2023-11-29 criteria provided, single submitter clinical testing
Athena Diagnostics RCV000040902 SCV001477093 benign not specified 2019-10-17 criteria provided, single submitter clinical testing
Molecular Genetics, Royal Melbourne Hospital RCV003993771 SCV004812421 likely benign TTN-related myopathy 2023-06-06 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000118798 SCV001740594 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000040902 SCV001921288 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000118798 SCV001928598 likely benign not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000040902 SCV001957300 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000040902 SCV001972521 benign not specified no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000118798 SCV002035355 likely benign not provided no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.