Submissions for variant NM_001267550.2(TTN):c.71723G>A (p.Gly23908Asp)

gnomAD frequency: 0.00021  dbSNP: rs540161344

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000156662	SCV000206383	uncertain significance	not specified	2015-01-14	criteria provided, single submitter	clinical testing	The p.Gly21340Asp variant in TTN has been identified by our laboratory in 1 adol escent with DCM, but has also been identified in 7/9800 African chromosomes by t he Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Computat ional prediction tools and conservation analyses suggest this variant may impact the protein, though this information is not predictive enough to determine path ogenicity. In summary, the clinical significance of the p.Gly21340Asp variant is uncertain.
Fulgent Genetics, Fulgent Genetics	RCV000764319	SCV000895338	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	2018-10-31	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000184787	SCV001476370	likely benign	not provided	2019-09-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000156662	SCV002571828	uncertain significance	not specified	2022-08-06	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002326891	SCV002638435	likely benign	Cardiovascular phenotype	2020-06-25	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.
Revvity Omics, Revvity	RCV000184787	SCV003825432	uncertain significance	not provided	2020-07-20	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000184787	SCV004225819	uncertain significance	not provided	2023-01-12	criteria provided, single submitter	clinical testing	PP3
GeneDx	RCV000184787	SCV000237499	not provided	not provided	2014-07-08	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 CARDIOMYOPATHY panel(s).