Submissions for variant NM_001267550.2(TTN):c.46489G>T (p.Val15497Phe)

gnomAD frequency: 0.00004  dbSNP: rs371299188

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000217743	SCV000272655	uncertain significance	not specified	2015-03-11	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Val12929Phe v ariant in TTN has not been previously reported in individuals with cardiomyopath y, but has been identified in 0.1% (10/8450) of East Asian chromosomes by the Ex ome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs371299 188). Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enoug h to determine pathogenicity. In summary, while the clinical significance of th e p.Val12929Phe variant is uncertain, its frequency suggests that it is more lik ely to be benign.
Invitae	RCV001079797	SCV000764545	likely benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-31	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000730718	SCV000858479	uncertain significance	not provided	2017-12-06	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001170842	SCV001333462	likely benign	Cardiomyopathy	2020-09-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000730718	SCV002504376	likely benign	not provided	2019-02-22	criteria provided, single submitter	clinical testing	See Variant Classification Assertion Criteria.
Ambry Genetics	RCV002408935	SCV002720703	likely benign	Cardiovascular phenotype	2020-05-12	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.
Revvity Omics, Revvity	RCV000730718	SCV003820318	uncertain significance	not provided	2023-12-12	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000730718	SCV001927178	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000217743	SCV001952382	benign	not specified		no assertion criteria provided	clinical testing