Submissions for variant NM_001267550.2(TTN):c.70815G>A (p.Val23605=)

gnomAD frequency: 0.00228  dbSNP: rs55847238

Total submissions: 22

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000040562	SCV000064253	benign	not specified	2012-01-25	criteria provided, single submitter	clinical testing
GeneDx	RCV000040562	SCV000169350	benign	not specified	2013-01-30	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV001082634	SCV000286812	benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000247125	SCV000319013	likely benign	Cardiovascular phenotype	2013-09-12	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
Eurofins Ntd Llc (ga)	RCV000040562	SCV000334478	likely benign	not specified	2015-08-18	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000328195	SCV000421999	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2J	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000362297	SCV000422000	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000270031	SCV000422001	benign	Tibial muscular dystrophy	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000389086	SCV000422003	uncertain significance	Early-onset myopathy with fatal cardiomyopathy	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000273614	SCV000422004	uncertain significance	Dilated cardiomyopathy 1G	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Genetic Services Laboratory, University of Chicago	RCV000040562	SCV000597642	likely benign	not specified	2016-12-23	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000513284	SCV000608997	likely benign	not provided	2024-03-01	criteria provided, single submitter	clinical testing	TTN: BP4, BP7
Athena Diagnostics	RCV000040562	SCV000616134	benign	not specified	2017-05-04	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000768941	SCV000900314	benign	Cardiomyopathy	2019-04-23	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000513284	SCV001159091	benign	not provided	2023-10-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000040562	SCV001362716	benign	not specified	2019-09-14	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000513284	SCV001743239	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000040562	SCV001920024	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000040562	SCV001927057	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000040562	SCV001953659	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000513284	SCV001971488	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000513284	SCV002036704	likely benign	not provided		no assertion criteria provided	clinical testing