ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.3241G>A (p.Ala1081Thr)

dbSNP: rs55914517
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 21
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 RCV000172732 SCV000051346 likely benign not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine,Mass General Brigham Personalized Medicine RCV000040201 SCV000063892 uncertain significance not specified 2014-07-21 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Ala1081Thr vari ant in TTN has been identified by our laboratory in 2 adults with HCM, including one who carries a pathogenic variant in another gene. This variant has been ide ntified in 0.1% (9/8600) of European American chromosomes by the NHLBI Exome Seq uencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs59914517). Computati onal prediction tools and conservation analysis do not provide strong support fo r or against an impact to the protein. In summary, while the clinical significan ce of the Ala1081Thr variant is uncertain, its frequency suggests that it is mor e likely to be benign.
GeneDx RCV000172732 SCV000237732 likely benign not provided 2020-07-14 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 17344846, 23861362)
Genetic Services Laboratory,University of Chicago RCV000040201 SCV000249254 uncertain significance not specified 2015-04-08 criteria provided, single submitter clinical testing
Invitae RCV001085560 SCV000286578 likely benign Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2021-12-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV000253970 SCV000318004 uncertain significance Cardiovascular phenotype 2012-11-19 criteria provided, single submitter clinical testing There is insufficient or conflicting evidence for classification of this alteration.
Eurofins NTD LLC (GA) RCV000040201 SCV000333906 likely benign not specified 2016-01-19 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV001129772 SCV001289315 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 Laboratory Services,Illumina RCV001132481 SCV001292141 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 Laboratory Services,Illumina RCV001132482 SCV001292142 uncertain significance 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 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 Laboratory Services,Illumina RCV001132483 SCV001292143 uncertain significance Autosomal recessive 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 Laboratory Services,Illumina RCV001132484 SCV001292144 uncertain significance Early-onset myopathy 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.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001170662 SCV001333256 likely benign Cardiomyopathy 2020-09-04 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001129772 SCV001369633 uncertain significance Tibial muscular dystrophy 2019-09-13 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP3,BP1.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000040201 SCV001426870 likely benign not specified 2020-07-20 criteria provided, single submitter clinical testing Variant summary: TTN c.3241G>A (p.Ala1081Thr) results in a non-conservative amino acid change located in the near Z-disk 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 0.00067 in 251122 control chromosomes in the gnomAD database, including 1 homozygote. The observed variant frequency is approximately 1.7- fold the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Dilated Cardiomyopathy phenotype (0.00039), suggesting that the variant is benign. c.3241G>A has been reported in the literature in at least one individual affected with Hypertrophic Cardiomyopathy (e.g. Campuzano_2015, Mademont-Soler_2017). These reports do not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. Co-occurrence with another pathogenic variant has been reported in the literature (MYBPC3 c.2512G>T, p.E838X; Mademont-Soler_2017), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments, including uncertain significance (n=3), likely benign (n=4), and benign (n=1). Based on the evidence outlined above, the variant was classified as likely benign.
CeGaT Center for Human Genetics Tuebingen RCV000172732 SCV001500699 likely benign not provided 2021-01-01 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000040201 SCV001880241 benign not specified 2020-10-15 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000172732 SCV001743765 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000172732 SCV001918801 likely benign not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000172732 SCV001953543 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000172732 SCV001972008 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.