Submissions for variant NM_001267550.2(TTN):c.55306G>A (p.Glu18436Lys)

gnomAD frequency: 0.00021  dbSNP: rs201510986

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000152302	SCV000201170	uncertain significance	not specified	2014-08-22	criteria provided, single submitter	clinical testing	The Glu15868Lys variant in TTN has not been previously reported in individuals w ith cardiomyopathy, but has been identified in 2/3642 African American chromosom es by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbS NP rs201510986). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the Glu15868Lys variant is uncertain.
Invitae	RCV000469348	SCV000542295	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2016-12-15	criteria provided, single submitter	clinical testing
GeneDx	RCV001528481	SCV000589587	likely benign	not provided	2020-03-18	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 25447171)
Ambry Genetics	RCV002433663	SCV002752334	uncertain significance	Cardiovascular phenotype	2019-12-30	criteria provided, single submitter	clinical testing	The p.E9371K variant (also known as c.28111G>A and under NM_133378.4: p.E15868K), located in coding exon 113 of the TTN gene, results from a G to A substitution at nucleotide position 28111. The glutamic acid at codon 9371 is replaced by lysine, an amino acid with similar properties. This alteration has been reported in a sudden cardiac death cohort in one subject who also had alterations in other cardiac-related genes (Campuzano O et al. Forensic Sci. Int., 2014 12;245:30-7). 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.
Revvity Omics, Revvity	RCV001528481	SCV004237116	uncertain significance	not provided	2023-06-30	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528481	SCV001740301	uncertain significance	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001528481	SCV001799186	uncertain significance	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001528481	SCV001932227	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001528481	SCV001971911	uncertain significance	not provided		no assertion criteria provided	clinical testing