ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.95134T>C (p.Cys31712Arg) (rs869320740)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000254991 SCV000322332 pathogenic not provided 2016-01-12 criteria provided, single submitter clinical testing The C30071R pathogenic variant in the TTN gene has been reported previously in association with myopathy with early respiratory failure (Ohlsson et al., 2012; Pfeffer et al., 2012; Toro et al., 2013; Yue et al., 2015). Functional studies show C30071R impairs solubility of the 119th fibronectin-3 domain, causing defective protein folding (Hedberg et al., 2014). The C30071R variant was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The C30071R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Cysteine are tolerated across species. We interpret C30071R as a pathogenic variant.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000254991 SCV000338332 pathogenic not provided 2016-01-08 criteria provided, single submitter clinical testing
Invitae RCV000627779 SCV000543100 pathogenic Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-08-27 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 31712 of the TTN protein (p.Cys31712Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is not present in population databases (ExAC no frequency). This variant is clearly defined as an autosomal dominant hereditary myopathy with early respiratory failure (HMERF) causative allele (PMID: 24980681). It is a common cause of HMERF in individuals of many different ancestries (PMID: 24444549, 25500009). This variant is also known as g.274375T4C (p.Cys30071Arg) in the literature. ClinVar contains an entry for this variant (Variation ID: 132133). Experimental studies have found that this missense change may interfere with the proper folding of the fibronectin III domain 119 of the TTN protein (PMID: 24636144). For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics Inc RCV000254991 SCV000616186 pathogenic not provided 2017-07-27 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768851 SCV000900224 pathogenic Cardiomyopathy 2017-05-23 criteria provided, single submitter clinical testing
GeneReviews RCV000119021 SCV000153723 pathogenic Myopathy, myofibrillar, 9, with early respiratory failure 2020-03-16 no assertion criteria provided literature only
OMIM RCV000119021 SCV000897722 pathogenic Myopathy, myofibrillar, 9, with early respiratory failure 2014-03-01 no assertion criteria provided literature only

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.