Submissions for variant NM_001267550.2(TTN):c.48953T>C (p.Ile16318Thr)

gnomAD frequency: 0.00094  dbSNP: rs72677243

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000172665	SCV000051471	likely benign	not provided	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000040295	SCV000063986	uncertain significance	not specified	2016-11-15	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Ile13750Thr v ariant in TTN has been identified by our laboratory in several individuals with various types of cardiomyopathy, did not segregate with disease in 1 relative wi th HCM, and has been identified in 0.2% (119/66356) of European chromosomes, inc luding 1 homozygote, by the Exome Aggregation Consortium (ExAC, http://exac.broa dinstitute.org; dbSNP rs72677243). Computational prediction tools and conservati on analysis suggest that the p.Ile13750Thr variant may impact the protein, thoug h this information is not predictive enough to determine pathogenicity. In summa ry, while the clinical significance of the p.Ile13750Thr variant is uncertain, i ts frequency suggests that it is more likely to be benign.
GeneDx	RCV000172665	SCV000237240	benign	not provided	2020-09-04	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 28144010, 27488758)
Genetic Services Laboratory, University of Chicago	RCV000040295	SCV000249260	likely benign	not specified	2015-03-09	criteria provided, single submitter	clinical testing
Invitae	RCV001083138	SCV000286693	likely benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000247886	SCV000318300	uncertain significance	Cardiovascular phenotype	2013-02-07	criteria provided, single submitter	clinical testing	There is insufficient or conflicting evidence for classification of this alteration.
Eurofins Ntd Llc (ga)	RCV000172665	SCV000332602	uncertain significance	not provided	2015-07-10	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000172665	SCV000844708	benign	not provided	2018-02-06	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000768997	SCV000900370	benign	Cardiomyopathy	2019-06-24	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000768997	SCV000995581	benign	Cardiomyopathy	2019-04-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001130555	SCV001290135	uncertain significance	Early-onset myopathy with fatal cardiomyopathy	2017-05-08	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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV000655929	SCV001290136	benign	Tibial muscular dystrophy	2017-05-08	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). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001131280	SCV001290896	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2017-05-08	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). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001131281	SCV001290897	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-04-27	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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001131282	SCV001290898	benign	Dilated cardiomyopathy 1G	2017-05-08	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.
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	RCV000040295	SCV001984158	likely benign	not specified	2019-12-12	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000172665	SCV002496590	benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	TTN: BS1, BS2
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000040295	SCV002819910	likely benign	not specified	2022-12-04	criteria provided, single submitter	clinical testing
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	RCV000655929	SCV000747737	uncertain significance	Tibial muscular dystrophy	2014-07-07	no assertion criteria provided	clinical testing	The observed variant c.22334T>C (p.I7445T) is reported in 1000 Genomes and ExAC databases with a minor allele frequency of 0.0004 and 0.0012 respectively. The in silico prediction of the above variant is disease causing by MutationTaster2, tolerated by SIFT and probably damaging by PolyPhen2.