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

gnomAD frequency: 0.00021  dbSNP: rs187460377

Total submissions: 8

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	2024-01-22	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.
Revvity Omics, Revvity	RCV000727232	SCV003820270	uncertain significance	not provided	2019-11-18	criteria provided, single submitter	clinical testing