ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.66086G>A (p.Arg22029His)

gnomAD frequency: 0.00009  dbSNP: rs72646868
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Total submissions: 8
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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 RCV000040503 SCV000064194 uncertain significance not specified 2012-12-11 criteria provided, single submitter clinical testing The Arg19461His variant in TTN has not been reported in the literature nor previ ously identified by our laboratory. This variant has been identified in 1/8218 E uropean American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS/; dbSNP rs72646868). Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein . Additional information is needed to fully assess the clinical significance of the Arg19461His variant.
GeneDx RCV000714070 SCV000237438 likely benign not provided 2018-11-08 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 28771489, 26567375)
Eurofins Ntd Llc (ga) RCV000714070 SCV000335246 uncertain significance not provided 2015-09-17 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000460102 SCV000542454 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2016-11-26 criteria provided, single submitter clinical testing
Athena Diagnostics RCV000714070 SCV000844737 uncertain significance not provided 2017-12-06 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000714070 SCV001474637 uncertain significance not provided 2019-11-14 criteria provided, single submitter clinical testing The TTN c.66086G>A; p.Arg22029His variant (rs72646868; ClinVar Variation ID: 47233) is rare in the general population (<1% allele frequency in the Genome Aggregation Database) and has not been reported in the medical literature in association with dilated cardiomyopathy (DCM) or other TTN-related disease. The clinical relevance of rare missense variants in this gene, which are identified on average once per individual sequenced in affected populations (Herman 2012), is not well understood. Yet, evidence suggests that the vast majority of such missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Thus, the clinical significance of the p.Arg22029His variant cannot be determined with certainty. References: Begay RL et al. Role of Titin Missense Variants in Dilated Cardiomyopathy. J Am Heart Assoc. 2015 Nov 13;4(11). Herman DS et al. Truncations of titin causing dilated cardiomyopathy. N Engl J Med. 2012 Feb 16;366(7):619-28.
Ambry Genetics RCV002362633 SCV002623904 uncertain significance Cardiovascular phenotype 2019-09-26 criteria provided, single submitter clinical testing The p.R12964H variant (also known as c.38891G>A), located in coding exon 141 of the TTN gene, results from a G to A substitution at nucleotide position 38891. The arginine at codon 12964 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV000714070 SCV003822811 uncertain significance not provided 2022-09-13 criteria provided, single submitter clinical testing

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