Submissions for variant NM_133379.5(TTN):c.14806A>T (p.Thr4936Ser)

gnomAD frequency: 0.00042  dbSNP: rs72648909

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000172432	SCV000055087	uncertain significance	not provided	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000041046	SCV000064737	likely benign	not specified	2021-04-28	criteria provided, single submitter	clinical testing	The p.Thr4936Ser variant in TTN is classified as likely benign because it has been identified in 0.09% (32/35326) of Latino chromosomes by gnomAD (http://gnomad.broadinstitute.org). It is also located in an exon that is not highly expressed in the heart and is only present in a transcript (Novex -3) whose function is unclear. ACMG/AMP Criteria applied: BP1, BS1.
Eurofins Ntd Llc (ga)	RCV000172432	SCV000702516	uncertain significance	not provided	2018-06-14	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000172432	SCV001153126	uncertain significance	not provided	2017-08-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002483024	SCV002787110	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9	2021-08-18	criteria provided, single submitter	clinical testing
GeneDx	RCV000172432	SCV000238134	not provided	not provided	2014-07-28	no assertion provided	clinical testing	Missense variants in the TTN gene are considered 'unclassified' if they are not previously reported in the literature and do not have >1% frequency in the population to be considered a polymorphism. Research indicates that truncating mutations in the TTN gene are expected to account for approximately 25% of familial and 18% of sporadic idiopathic DCM; however, truncating variants in the TTN gene have been reported in approximately 3% of reported control alleles. There has been little investigation into non-truncating variants. (Herman D et al. Truncations of titin causing dilated cardiomyopathy. N Eng J Med 366:619-628, 2012) The variant is found in DCM-CRDM panel(s).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000172432	SCV001744199	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000172432	SCV001923031	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000172432	SCV001955984	likely benign	not provided		no assertion criteria provided	clinical testing