ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.49363A>G (p.Thr16455Ala)

gnomAD frequency: 0.00009  dbSNP: rs374543277
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000248196 SCV000319022 uncertain significance Cardiovascular phenotype 2013-11-18 criteria provided, single submitter clinical testing The p.T13887A variant (also known as c.41659A>G) is located in coding exon 211 of the TTNgene. This alteration results from an A to G substitution at nucleotide position 41659. The threonine at codon 13887 is replaced by alanine, an amino acid with some similar properties.Based on data from the NHLBI Exome Sequencing Project (ESP), the G-allele has an overall frequency of approximately0.02% (2/12184), having been observed in0.02% (2/8304)of European American alleles, and not observed in 3880 African American alleles studied.This variant was not reported in population-based cohorts in the Database of Single Nucleotide Polymorphisms (dbSNP) or the 1000 Genomes Project. Based on protein sequence alignment, this amino acid position isconserved through amphibians, but is not conserved in lower vertebrate species.In addition, this alteration is predicted to be possibly damaging by PolyPhen in silico analysis.Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Invitae RCV000458087 SCV000542322 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2016-07-11 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000184579 SCV000701215 uncertain significance not provided 2017-01-26 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000184579 SCV002770624 uncertain significance not provided 2022-07-18 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002485242 SCV002787124 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 2021-10-26 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000184579 SCV003818473 uncertain significance not provided 2022-03-15 criteria provided, single submitter clinical testing
GeneDx RCV000184579 SCV000237247 not provided not provided 2013-10-03 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 DCM panel(s).

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