ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.16288C>T (p.Arg5430Ter) (rs772235481)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000312986 SCV000334048 uncertain significance not provided 2015-09-03 criteria provided, single submitter clinical testing
Invitae RCV000814903 SCV000955340 uncertain significance Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2019-10-03 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the TTN gene (p.Arg5430*). While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with early-onset atrial fibrillation (PMID: 30535219). ClinVar contains an entry for this variant (Variation ID: 282527). This variant is located in the I band of TTN (PMID: 25589632). Truncating variants in this region have been shown to be highly prevalent in the general population and unaffected individuals (PMID: 26701604, 22335739). However, truncating variants in this region have also been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Baylor Genetics RCV000415222 SCV000328733 pathogenic Dilated cardiomyopathy 1G; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Familial hypertrophic cardiomyopathy 9 2015-07-04 no assertion criteria provided clinical testing Our laboratory reported two molecular diagnoses in NOTCH1 (NM_017617.3, c.6348C>G) and TTN (NM_133378.3, c.12556C>T)in one individual with reported features of delayed speech, dysmorphic features (hypertelorism with widened nasal bridge, over folded helices and prominent long philtrum), congenital heart disease (tricuspid valve dysplasia, sinus of valsalva dilatation and atrial enlargement), pulmonary lymphangiectasia, and transient neonatal cholestasis. The variant in NOTCH1 is predicted to cause a nonsense mutation and is categorized as deleterious by ACMGG guidelines [PMID: 18414213].

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