Submissions for variant NM_001267550.2(TTN):c.49937G>A (p.Arg16646Gln)

gnomAD frequency: 0.00006  dbSNP: rs746384579

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000642726	SCV000764413	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-12-06	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with glutamine at codon 16646 of the TTN protein (p.Arg16646Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs746384579, ExAC 0.01%). This variant has not been reported in the literature in individuals with TTN-related disease. This variant identified in the TTN gene is located in the A band of the resulting protein (PMID: 25589632). It is unclear how this variant impacts the function of this protein. Algorithms developed to predict the effect of missense changes on protein structure and function are unavailable for the TTN gene. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a novel missense change with unknown impact on protein function. Missense variants in this region of the TTN gene are typically not causative for cardiac disease, but may be relevant for neuromuscular disorders. However, the available evidence is currently insufficient to determine this variant’s role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Athena Diagnostics	RCV000993447	SCV001146420	uncertain significance	not provided	2019-06-06	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000993447	SCV003822242	uncertain significance	not provided	2019-04-17	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000993447	SCV001921427	uncertain significance	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000993447	SCV001931439	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000993447	SCV001952979	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000993447	SCV001970871	uncertain significance	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000993447	SCV001978500	uncertain significance	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000993447	SCV002036302	uncertain significance	not provided		no assertion criteria provided	clinical testing