Submissions for variant NM_001267550.2(TTN):c.12748G>A (p.Val4250Met)

gnomAD frequency: 0.00086  dbSNP: rs201437752

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000172703	SCV000051480	likely benign	not provided	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154998	SCV000204680	likely benign	not specified	2015-05-21	criteria provided, single submitter	clinical testing	p.Val4012Met in exon 45B in TTN: This variant is not expected to have clinical s ignificance due to a lack of conservation across species, including mammals. Of note, 5 mammals (bushbaby, squirrel, hedgehog, aardvark, and Tasmanian devil) ha ve a methionine (Met) at this position despite amino acid conservation at nearby positions. It has been identified in 0.1% (93/66496) of European chromosomes, i ncluding 1 homozygote, by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs201437752).
GeneDx	RCV000172703	SCV000238180	likely benign	not provided	2021-02-26	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000172703	SCV000336234	uncertain significance	not provided	2018-06-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000621842	SCV000735760	likely benign	Cardiovascular phenotype	2018-08-23	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.
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852922	SCV000995664	likely benign	Primary dilated cardiomyopathy; Cardiomyopathy	2019-05-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001085765	SCV001001863	likely benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000172703	SCV001153098	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	TTN: BP4
Athena Diagnostics	RCV000154998	SCV001880209	benign	not specified	2020-10-19	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798510	SCV002042363	benign	Cardiomyopathy	2020-07-02	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000172703	SCV001743372	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000154998	SCV001919448	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000172703	SCV001928389	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000154998	SCV001956911	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000172703	SCV001971663	likely benign	not provided		no assertion criteria provided	clinical testing