Submissions for variant NM_006073.4(TRDN):c.1367A>G (p.Gln456Arg)

gnomAD frequency: 0.00128  dbSNP: rs200243235

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000214726	SCV000272540	uncertain significance	not specified	2016-02-16	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Gln457Arg var iant in TRDN has not been previously reported in individuals with cardiomyopathy , but has been identified in 0.2% (111/65742) of European chromosomes by the Exo me Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs2002432 35). Computational prediction tools and conservation analysis do not provide str ong support for or against an impact to the protein. In summary, while the clini cal significance of the p.Gln457Arg variant is uncertain, its frequency suggests that it is more likely to be benign.
Invitae	RCV002518213	SCV000289127	likely benign	Catecholaminergic polymorphic ventricular tachycardia 1	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000766958	SCV000532894	uncertain significance	not provided	2023-05-09	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Reported in an individual with DCM; described as Q457R (Burstein et al., 2021); This variant is associated with the following publications: (PMID: 35932045, 23035052, 32746448)
Ambry Genetics	RCV000620191	SCV000736280	likely benign	Cardiovascular phenotype	2021-05-04	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV000766958	SCV004032696	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	TRDN: BP4
KardioGenetik, Herz- und Diabeteszentrum NRW	RCV003327383	SCV004034987	uncertain significance	Catecholaminergic polymorphic ventricular tachycardia 5	2023-08-30	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV003327383	SCV004563223	uncertain significance	Catecholaminergic polymorphic ventricular tachycardia 5	2023-10-23	criteria provided, single submitter	clinical testing	The TRDN c.1367A>G; p.Gln456Arg variant (rs200243235), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 229345). This variant is found in the non-Finnish European population with an allele frequency of 0.2% (243/127,472 alleles) in the Genome Aggregation Database. The glutamine at codon 456 is weakly conserved, but computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Due to limited information, the clinical significance of the p.Gln456Arg variant is uncertain at this time.
Clinical Genetics, Academic Medical Center	RCV000766958	SCV001923413	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000766958	SCV001953060	likely benign	not provided		no assertion criteria provided	clinical testing