Submissions for variant NM_001267550.2(TTN):c.71981C>T (p.Ala23994Val)

gnomAD frequency: 0.00003  dbSNP: rs772886864

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001706157	SCV000237503	likely benign	not provided	2020-11-12	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000217716	SCV000272744	uncertain significance	not specified	2015-03-05	criteria provided, single submitter	clinical testing	The p.Ala21426Val variant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 1/66640 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Comput ational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Ala21426Val variant is uncertain.
Ambry Genetics	RCV002327006	SCV002636105	likely benign	Cardiovascular phenotype	2021-11-09	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	RCV001706157	SCV001919863	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001706157	SCV001972201	uncertain significance	not provided		no assertion criteria provided	clinical testing