ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.48164G>A (p.Arg16055His)

gnomAD frequency: 0.00003  dbSNP: rs72677238
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001704899 SCV000237229 likely benign not provided 2021-05-17 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 31983221)
Invitae RCV000227076 SCV000286690 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2016-06-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV000254392 SCV000320211 uncertain significance Cardiovascular phenotype 2015-09-28 criteria provided, single submitter clinical testing The p.R6990H variant (also known as c.20969G>A), located in coding exon 84 of the TTN gene, results from a G to A substitution at nucleotide position 20969. The arginine at codon 6990 is replaced by histidine, an amino acid with highly similar properties. This variant was previously reported in the SNPDatabase as rs72677238. Based on data from the NHLBI Exome Sequencing Project (ESP), the A allele has an overall frequency of approximately 0.02% (2/11988) total alleles studied and 0.02% (2/8230) European American alleles. 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 variant remains unclear.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000184566 SCV001158438 uncertain significance not specified 2019-05-26 criteria provided, single submitter clinical testing The TTN c.48164G>A; p.Arg16055His variant (rs72677238; ClinVar Variation ID: 202663) 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.Arg16055His 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 and Hamdani. Gigantic business: titin properties and function through thick and thin. Circ Res 2014; 114(6): 1052-1068.
Revvity Omics, Revvity RCV001704899 SCV003826628 uncertain significance not provided 2020-11-13 criteria provided, single submitter clinical testing

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