ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.58939G>A (p.Gly19647Arg)

gnomAD frequency: 0.00004  dbSNP: rs201430346
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001810635 SCV001474566 uncertain significance not provided 2020-03-26 criteria provided, single submitter clinical testing The TTN c.58939G>A; p.Gly19647Arg variant (rs201430346) 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.Gly19647Arg 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. Linke WA and Hamdani N. Gigantic business: titin properties and function through thick and thin. Circ Res 2014; 114(6): 1052-1068.
Ambry Genetics RCV002322178 SCV002609731 uncertain significance Cardiovascular phenotype 2019-03-29 criteria provided, single submitter clinical testing The p.G10582R variant (also known as c.31744G>A), located in coding exon 126 of the TTN gene, results from a G to A substitution at nucleotide position 31744. The glycine at codon 10582 is replaced by arginine, an amino acid with dissimilar 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.
Fulgent Genetics, Fulgent Genetics RCV002486078 SCV002785933 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 2021-10-11 criteria provided, single submitter clinical testing

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