Submissions for variant NM_001267550.2(TTN):c.66172C>T (p.Arg22058Cys)

gnomAD frequency: 0.00044  dbSNP: rs199643269

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000215351	SCV000272726	uncertain significance	not specified	2017-06-28	criteria provided, single submitter	clinical testing	The p.Arg19490Cys variant in TTN has been reported by our laboratory in 1 indivi dual with DCM, has been identified in 0.09% (20/23668) of African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/; dbS NP rs199643269), and has been reported in ClinVar (Variation ID: 229491). While truncating variants in TTN are strongly associated with DCM (Herman 2012), the r ole of missense variants and in-frame deletions/insertions has yet to be elucida ted. Computational prediction tools and conservation analysis do not provide str ong support for or against an impact to the protein. In summary, the clinical si gnificance of the p.Arg19490Cys variant is uncertain.
Invitae	RCV000459142	SCV000543078	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-12-12	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000727313	SCV000707479	uncertain significance	not provided	2017-04-06	criteria provided, single submitter	clinical testing
GeneDx	RCV000215351	SCV000716841	likely benign	not specified	2017-03-15	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV002354614	SCV002620674	likely benign	Cardiovascular phenotype	2020-02-12	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Clinical Genetics, Academic Medical Center	RCV000727313	SCV001917174	uncertain significance	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000727313	SCV001963070	uncertain significance	not provided		no assertion criteria provided	clinical testing