ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.10046C>T (p.Thr3349Ile)

gnomAD frequency: 0.00003  dbSNP: rs727503678
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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, Mass General Brigham Personalized Medicine RCV000152475 SCV000201600 uncertain significance not specified 2014-04-16 criteria provided, single submitter clinical testing The Thr3349Ile variant in TTN has not been reported in individuals with cardiomy opathy or in large population studies. Computational prediction tools and conser vation analysis do not provide strong support for or against an impact to the pr otein. Additional information is needed to fully assess the clinical significan ce of the variant.
Invitae RCV000458217 SCV000542889 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-07-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV002381482 SCV002691300 uncertain significance Cardiovascular phenotype 2019-03-11 criteria provided, single submitter clinical testing The p.T3303I variant (also known as c.9908C>T), located in coding exon 41 of the TTN gene, results from a C to T substitution at nucleotide position 9908. The threonine at codon 3303 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002483322 SCV002794133 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9 2021-11-10 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000185219 SCV003819853 uncertain significance not provided 2020-08-17 criteria provided, single submitter clinical testing
GeneDx RCV000185219 SCV000238072 not provided not provided 2014-05-28 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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