ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.88984G>A (p.Gly29662Ser)

gnomAD frequency: 0.00021  dbSNP: rs187460377
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Total submissions: 7
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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 RCV000154899 SCV000204581 uncertain significance not specified 2014-09-29 criteria provided, single submitter clinical testing The Gly27094Ser variant in TTN has been identified in our lab in 1 individual wi th infant-onset DCM. This variant has also been identified in 1/3844 African Ame rican chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washingto n.edu/EVS/) and in 1/122 African American chromosomes by the 1000 Genomes Projec t (dbSNP rs187460377). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summar y, the clinical significance of the Gly27094Ser variant is uncertain.
GeneDx RCV000727232 SCV000237713 likely benign not provided 2020-07-15 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 28704380)
Invitae RCV001079791 SCV000554992 likely benign Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2021-12-02 criteria provided, single submitter clinical testing
Eurofins NTD LLC (GA) RCV000727232 SCV000706793 uncertain significance not provided 2018-07-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV000618633 SCV000736113 uncertain significance Cardiovascular phenotype 2017-11-20 criteria provided, single submitter clinical testing The p.G20597S variant (also known as c.61789G>A), located in coding exon 160 of the TTN gene, results from a G to A substitution at nucleotide position 61789. The glycine at codon 20597 is replaced by serine, an amino acid with similar properties. This alteration has been reported (as NM_001267550.1:c.88984G>A p.G29662S) in a sudden unexplained death case; however, clinical details were limited (Suktitipat B et al. PLoS ONE, 2017 Jul;12:e0180056). 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.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769893 SCV000901319 benign Cardiomyopathy 2020-06-26 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000727232 SCV001471015 uncertain significance not provided 2020-08-23 criteria provided, single submitter clinical testing The TTN c.88984G>A, p.Gly29662Ser variant [(rs187460377; ClinVar Variation ID: 178174) 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.Gly29662Ser variant cannot be determined with certainty.

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