ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.100400T>G (p.Val33467Gly) (rs200166942)

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
Ambry Genetics RCV000621516 SCV000736544 uncertain significance Cardiovascular phenotype 2016-01-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient or conflicting evidence
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768836 SCV000900209 uncertain significance Cardiomyopathy 2017-07-14 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724741 SCV000229361 uncertain significance not provided 2018-05-31 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764299 SCV000895318 uncertain significance Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J; Distal myopathy Markesbery-Griggs type; Hereditary myopathy with early respiratory failure; Myopathy, early-onset, with fatal cardiomyopathy; Familial hypertrophic cardiomyopathy 9 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000152165 SCV000237881 uncertain significance not specified 2017-06-20 criteria provided, single submitter clinical testing The V31826G variant of uncertain significance in the TTN gene, also denoted as V33467G due to the use of an alternate transcript, has been reported in an individual diagnosed with HMERF who also harbored a second variant in the TTN gene (Evila et al., 2016); however, further segregation studies were not described, including confirmation of whether these variants were on the same allele or opposite alleles. The V31826G variant is also classified as a variant of uncertain significance by other clinical laboratories (ClinVar SCV000200885.3, SCV000229361.3, SCV000542401.1; Landrum et al., 2016). Additionally, this variant has been observed in 38/66210 (0.06%) alleles from individuals of Non-Finnish European ancestry in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The V31826G variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Furthermore, although V31826G is located in the A-band region of the titin protein, the majority of pathogenic variants in the TTN gene associated with DCM are truncating variants in this region (Herman et al., 2012). Nevertheless, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function.
Illumina Clinical Services Laboratory,Illumina RCV000277427 SCV000420295 uncertain significance Dilated Cardiomyopathy, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000324927 SCV000420296 uncertain significance Hereditary myopathy with early respiratory failure 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000381891 SCV000420297 uncertain significance Limb-Girdle Muscular Dystrophy, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000290262 SCV000420298 uncertain significance Hypertrophic cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000328826 SCV000420299 uncertain significance Myopathy, early-onset, with fatal cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000376472 SCV000420300 uncertain significance Distal myopathy Markesbery-Griggs type 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000471295 SCV000542401 uncertain significance Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2017-10-30 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000152165 SCV000200885 uncertain significance not specified 2014-12-23 criteria provided, single submitter clinical testing The p.Val30899Gly variant in TTN has been identified by our laboratory in 2 Cauc asian individuals with DCM and 1 Caucasian individual with HCM. However, the ind ividual with HCM also carried another pathogenic variant that was sufficient to explain their disease. The p.Val30899Gly variant has also been identified in 40/ 67148 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exa c.broadinstitute.org; dbSNP rs200166942). Computational prediction tools and con servation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Val30899Gly variant is uncertain.

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.