Submissions for variant NM_001267550.2(TTN):c.16313A>G (p.Lys5438Arg)

gnomAD frequency: 0.00061  dbSNP: rs190636272

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000172406	SCV000055069	uncertain significance	not provided	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039885	SCV000063576	uncertain significance	not specified	2016-01-29	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Lys4194Arg va riant in TTN has been previously identified by our laboratory in 2 adults with D CM, 1 adult with HCM, and 1 infant with HCM and LV enlargement. This variant has been identified in 0.1% (85/66092) of European chromosomes by the Exome Aggrega tion Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs190636272). Compu tational prediction tools and conservation analysis do not provide strong suppor t for or against an impact to the protein. In summary, while the clinical signif icance of the p.Lys4194Arg variant is uncertain, its frequency suggests that it is more likely to be benign.
GeneDx	RCV000172406	SCV000238229	likely benign	not provided	2020-07-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080301	SCV000286462	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)	RCV000172406	SCV000335926	uncertain significance	not provided	2018-05-21	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000039885	SCV000597706	uncertain significance	not specified	2016-05-23	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001130570	SCV001290151	benign	Tibial muscular dystrophy	2017-10-02	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001130571	SCV001290152	uncertain significance	Dilated cardiomyopathy 1G	2017-10-02	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001130572	SCV001290153	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2017-10-02	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001130573	SCV001290154	uncertain significance	Early-onset myopathy with fatal cardiomyopathy	2017-10-02	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001135657	SCV001295446	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-10-02	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149638	SCV003838662	benign	Cardiomyopathy	2021-10-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000039885	SCV004099910	likely benign	not specified	2023-09-16	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000172406	SCV004225914	uncertain significance	not provided	2023-03-30	criteria provided, single submitter	clinical testing	BP4
Clinical Genetics, Academic Medical Center	RCV000039885	SCV001918889	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000172406	SCV001957511	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000172406	SCV001966134	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004541134	SCV004764364	likely benign	TTN-related disorder	2024-01-02	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).