ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.103363C>T (p.Arg34455Cys) (rs72629785)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 13
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000040928 SCV000054866 benign not specified 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000040928 SCV000064619 benign not specified 2015-11-13 criteria provided, single submitter clinical testing p.Arg31887Cys in exon 307 of TTN: This variant is not expected to have clinical significance because it has been identified in 1% (95/9792) of African chromosom es including 3 homozygotes by the Exome Aggregation Consortium (ExAC, http://exa c.broadinstitute.org; dbSNP rs72629785).
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000040928 SCV000114505 benign not specified 2013-04-22 criteria provided, single submitter clinical testing
GeneDx RCV000040928 SCV000237911 benign not specified 2016-11-28 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 RCV001081893 SCV000555647 benign Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-11-28 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000710275 SCV000615966 likely benign not provided 2018-01-26 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768834 SCV000900207 likely benign Cardiomyopathy 2016-11-09 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001133967 SCV001293684 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.
Illumina Clinical Services Laboratory,Illumina RCV001133968 SCV001293685 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 RCV001133969 SCV001293686 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 RCV001133970 SCV001293687 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). 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 RCV001135483 SCV001295265 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000040928 SCV001431982 benign not specified 2020-08-31 criteria provided, single submitter clinical testing Variant summary: TTN c.95659C>T (p.Arg31887Cys) results in a non-conservative amino acid change located in the M-band region (cardiodb.org) 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 0.00072 in 248602 control chromosomes, predominantly at a frequency of 0.0095 within the African or African-American subpopulation in the gnomAD database, including 3 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 24-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 African or African-American origin. c.95659C>T has been reported in the literature in individuals affected with Dilated Cardiomyopathy (e.g. Pugh_2014, Tobita_2018). 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. Seven other ClinVar submitters (evaluation after 2014) have cited the variant as benign/likely benign (n=6) and uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as benign.

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.