ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.21656C>T (p.Ser7219Phe) (rs201029552)

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
Ambry Genetics RCV000251604 SCV000318161 uncertain significance Inborn genetic diseases 2014-06-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: UNCERTAIN: Alteration(s) of Uncertain Clinical Significance Detected
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770079 SCV000901505 uncertain significance Cardiomyopathy 2016-08-09 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725490 SCV000700993 uncertain significance not provided 2016-11-17 criteria provided, single submitter clinical testing
GeneDx RCV000213535 SCV000238300 uncertain significance not specified 2015-11-23 criteria provided, single submitter clinical testing Missense variants in the TTN gene are considered 'unclassified' if they are not previously reported in the literature and do not have >1% frequency in the population to be considered a polymorphism. Research indicates that truncating mutations in the TTN gene are expected to account for approximately 25% of familial and 18% of sporadic idiopathic DCM; however, truncating variants in the TTN gene have been reported in approximately 3% of reported control alleles. There has been little investigation into non-truncating variants. (Herman D et al. Truncations of titin causing dilated cardiomyopathy. N Eng J Med 366:619-628, 2012) The variant is found in CARDIOMYOPATHY panel(s).
Illumina Clinical Services Laboratory,Illumina RCV000296518 SCV000424340 uncertain significance Limb-Girdle Muscular Dystrophy, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000335093 SCV000424341 uncertain significance Hereditary myopathy with early respiratory failure 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000401816 SCV000424342 uncertain significance Myopathy, early-onset, with fatal cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000299959 SCV000424343 uncertain significance Hypertrophic cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000338709 SCV000424344 uncertain significance Dilated Cardiomyopathy, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000406874 SCV000424345 uncertain significance Distal myopathy Markesbery-Griggs type 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000470210 SCV000542321 uncertain significance Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2018-01-04 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000213535 SCV000272594 uncertain significance not specified 2015-03-24 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Ser5975Phe va riant in TTN has not been previously reported in individuals with cardiomyopathy , but has been identified in 17/65874 European chromosomes by the Exome Aggregat ion Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs201029552). Serine (Ser) at position 5975 is not conserved in evolutionarily distant species and s everal mammals (pig, horse, white rhinoceros and elephant) carry a phenylalanine (Phe) at this position, supporting that this change may be tolerated. Additiona l computational prediction tools suggest that this variant may not impact the pr otein, though this information is not predictive enough to rule out pathogenicit y. In summary, while the clinical significance of the p.Ser5975Phe variant is un certain, the presence of the variant amino acid in multiple mammals suggests tha t it is more likely to be 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.