Submissions for variant NM_001267550.2(TTN):c.102782C>A (p.Thr34261Asn)

gnomAD frequency: 0.00001  dbSNP: rs985229219

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001320592	SCV001511386	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-10-10	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 34261 of the TTN protein (p.Thr34261Asn). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of TTN-related conditions (PMID: 23975875). ClinVar contains an entry for this variant (Variation ID: 1020927). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant is located in the M band of TTN (PMID: 25589632). Non-truncating variants in this region may be relevant for neuromuscular disorders, but have not been definitively shown to cause cardiomyopathy (PMID: 23975875). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV002395698	SCV002670870	uncertain significance	Cardiovascular phenotype	2020-05-28	criteria provided, single submitter	clinical testing	The p.T25196N variant (also known as c.75587C>A), located in coding exon 185 of the TTN gene, results from a C to A substitution at nucleotide position 75587. The threonine at codon 25196 is replaced by asparagine, 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003486977	SCV004240228	likely benign	Cardiomyopathy	2023-05-03	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV001699532	SCV001925088	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001699532	SCV001968362	uncertain significance	not provided		no assertion criteria provided	clinical testing