ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.16621+7A>T (rs10200398)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 12
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000039889 SCV000063580 benign not specified 2012-03-14 criteria provided, single submitter clinical testing 12889+7A>T in intron 53 of TTN: This variant is not expected to have clinical si gnificance because it is not located within the splice consensus sequence and ha s been identified in 0.4% (13/3156) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/ EVS; dbSNP rs10200398).
GeneDx RCV000039889 SCV000236735 benign not specified 2014-09-04 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000039889 SCV000336431 benign not specified 2016-02-22 criteria provided, single submitter clinical testing
Invitae RCV001085418 SCV000555365 benign Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-11-27 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000039889 SCV000616007 benign not specified 2017-06-06 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000474528 SCV001153080 likely benign not provided 2017-05-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001130461 SCV001290037 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 RCV001135531 SCV001295313 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 RCV001135532 SCV001295314 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 RCV001135533 SCV001295315 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 RCV001135534 SCV001295316 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000039889 SCV001554605 benign not specified 2021-03-25 criteria provided, single submitter clinical testing Variant summary: TTN c.12889+7A>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 2/3 computational tools predict no significant impact on normal splicing, while one predicts the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00071 in 238564 control chromosomes, predominantly at a frequency of 0.0042 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 10-fold of 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. To our knowledge, no occurrence of c.12889+7A>T in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and all of them classified the variant as benign (n=4) / likely benign (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.