ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.100649G>A (p.Gly33550Asp)

gnomAD frequency: 0.00001  dbSNP: rs370253076
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000556309 SCV000642496 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-01-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000617950 SCV000737126 uncertain significance Cardiovascular phenotype 2020-01-09 criteria provided, single submitter clinical testing The p.G24485D variant (also known as c.73454G>A), located in coding exon 184 of the TTN gene, results from a G to A substitution at nucleotide position 73454. The glycine at codon 24485 is replaced by aspartic acid, an amino acid with similar 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001811050 SCV002049505 uncertain significance not provided 2021-02-04 criteria provided, single submitter clinical testing The TTN c.100649G>A; p.Gly33550Asp variant (rs370253076; ClinVar Variation ID: 466685) is rare in the general population (<0.2% 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.Gly33550Asp 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.
Revvity Omics, Revvity Omics RCV001811050 SCV003822965 uncertain significance not provided 2020-03-09 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001811050 SCV004225777 uncertain significance not provided 2022-02-03 criteria provided, single submitter clinical testing PM2_supporting

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