ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.63463C>T (p.Arg21155Cys)

gnomAD frequency: 0.00004  dbSNP: rs374727686
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000152260 SCV007338854 uncertain significance not specified 2025-12-30 criteria provided, single submitter clinical testing Variant summary: TTN c.55759C>T (p.Arg18587Cys) results in a non-conservative amino acid change in the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change. The variant allele was found at a frequency of 2.5e-05 in 240280 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.55759C>T in individuals affected with TTN-related conditions and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 165907). Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics RCV002460047 SCV002618002 uncertain significance Cardiovascular phenotype 2020-01-17 criteria provided, single submitter clinical testing The p.R12090C variant (also known as c.36268C>T), located in coding exon 132 of the TTN gene, results from a C to T substitution at nucleotide position 36268. The arginine at codon 12090 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly 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.
GeneDx RCV000724176 SCV000981778 likely benign not provided 2018-03-15 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp RCV000460153 SCV000542580 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-05-03 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000724176 SCV000228291 uncertain significance not provided 2015-06-05 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000152260 SCV000201094 uncertain significance not specified 2014-11-28 criteria provided, single submitter clinical testing The p.Arg18587Cys variant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 1/3770 of African American chro mosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/ ; dbSNP rs374727686). Computational prediction tools and conservation analysis s uggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significa nce of the p.Arg18587Cys variant is uncertain.

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