Submissions for variant NM_001267550.2(TTN):c.82754C>A (p.Ser27585Tyr)

gnomAD frequency: 0.00010  dbSNP: rs72648215

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000725384	SCV000237632	likely benign	not provided	2021-06-09	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000222951	SCV000272774	uncertain significance	not specified	2014-12-18	criteria provided, single submitter	clinical testing	The p.Ser25017Tyr variant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 11/67626 European chromosomes b y the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs72648215). Computational prediction tools and conservation analysis do not pro vide strong support for or against an impact to the protein. In summary, the cli nical significance of the p.Ser25017Tyr variant is uncertain.
Invitae	RCV000234626	SCV000286864	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2016-02-26	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000725384	SCV000700958	uncertain significance	not provided	2017-01-03	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000725384	SCV003825491	uncertain significance	not provided	2019-12-24	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003927716	SCV004742649	uncertain significance	TTN-related condition	2024-02-04	criteria provided, single submitter	clinical testing	The TTN c.82754C>A variant is predicted to result in the amino acid substitution p.Ser27585Tyr. This variant was reported in a dilated cardiomyopathy cohort; however, no additional studies were performed to help assess the pathogenicity of this variant (Begay et al. 2015. PubMed ID: 26567375). This variant is reported in 0.020% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Practice for Gait Abnormalities, David Pomarino, Competency Network Toe Walking c/o Practice Pomarino	RCV002227935	SCV002507282	likely pathogenic	Tip-toe gait		no assertion criteria provided	clinical testing