Submissions for variant NM_001267550.2(TTN):c.29230C>T (p.Arg9744Cys)

gnomAD frequency: 0.00004  dbSNP: rs375266859

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000040090	SCV000063781	uncertain significance	not specified	2012-07-02	criteria provided, single submitter	clinical testing	The Arg8500Cys variant in TTN has not been reported in the literature, but has b een identified in 1 individual with DCM tested by our laboratory. This variant h as not been identified in a very large and broad population by the NHLBI Exome S equencing Project (http://evs.gs.washington.edu/EVS). This low frequency is cons istent with a disease causing role, but insufficient to establish this with conf idence. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Additional information is needed to fully assess the cli nical significance of the Arg8500Cys variant.
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000415299	SCV000492926	likely benign	Sudden cardiac death; Cardiac arrest	2014-01-08	criteria provided, single submitter	clinical testing
Invitae	RCV000530713	SCV000642942	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-03-15	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000730819	SCV000858583	uncertain significance	not provided	2017-12-11	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769897	SCV000901323	uncertain significance	Cardiomyopathy	2016-11-16	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001134853	SCV001294612	uncertain significance	Early-onset myopathy with fatal cardiomyopathy	2017-04-28	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	RCV001134854	SCV001294613	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-04-28	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	RCV001134855	SCV001294614	likely benign	Tibial muscular dystrophy	2017-04-28	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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV001134856	SCV001294615	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2017-04-28	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	RCV001134857	SCV001294616	uncertain significance	Dilated cardiomyopathy 1G	2017-04-28	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.
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001134855	SCV001369269	likely benign	Tibial muscular dystrophy	2016-01-01	criteria provided, single submitter	clinical testing	This variant was classified as: Likely benign.
GeneDx	RCV000730819	SCV001771753	likely benign	not provided	2021-04-30	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 19608031)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000040090	SCV002570995	uncertain significance	not specified	2022-07-10	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000730819	SCV002770577	uncertain significance	not provided	2021-08-20	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000730819	SCV004033824	uncertain significance	not provided	2023-08-01	criteria provided, single submitter	clinical testing	TTN: PM2, PM3:Supporting