ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.66391A>G (p.Thr22131Ala) (rs140842479)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000040504 SCV000064195 uncertain significance not specified 2015-01-14 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Thr19563Ala v ariant in TTN has been identified by our laboratory in 1 adult with DCM, 1 adole scent with DCM, and 1 adolescent with LVNC. This variant has also been identifie d in 0.1% (16/9802) of African chromosomes by the Exome Aggregation Consortium ( ExAC, http://exac.broadinstitute.org; dbSNP rs140842479). Threonine (Thr) at po sition 19563 is not conserved in mammals or evolutionary distant species and add itional computational prediction tools do not provide strong evidence for or aga inst an impact to the protein. In summary, while the clinical significance of th e p.Thr19563Ala variant is uncertain, its frequency suggests that it is more lik ely to be benign.
Fulgent Genetics,Fulgent Genetics RCV000765558 SCV000896873 uncertain significance Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Myopathy, early-onset, with fatal cardiomyopathy; Familial hypertrophic cardiomyopathy 9 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV001088816 SCV001006079 likely benign Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-10-18 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000184735 SCV001249864 uncertain significance not provided 2019-11-01 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000184735 SCV001476357 likely benign not provided 2019-09-26 criteria provided, single submitter clinical testing
GeneDx RCV000184735 SCV000237439 not provided not provided 2014-07-08 no assertion provided 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).

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