Submissions for variant NM_001267550.2(TTN):c.89386G>A (p.Val29796Met)

gnomAD frequency: 0.00066  dbSNP: rs72648237

Total submissions: 20

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000082442	SCV000054902	uncertain significance	not provided	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154897	SCV000204579	likely benign	not specified	2015-04-09	criteria provided, single submitter	clinical testing	p.Val27228Met in exon 283 of TTN: This variant is not expected to have clinical significance because it has been identified in 0.5% (89/16510) of South Asian ch romosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute. org; dbSNP rs72648237).
GeneDx	RCV000082442	SCV000237715	benign	not provided	2018-08-16	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 23396983, 23861362)
Ambry Genetics	RCV000246600	SCV000318947	likely benign	Cardiovascular phenotype	2019-06-07	criteria provided, single submitter	clinical testing	Subpopulation frequency in support of benign classification
Eurofins Ntd Llc (ga)	RCV000154897	SCV000332474	likely benign	not specified	2015-07-02	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000283095	SCV000420991	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2J	2018-01-13	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	RCV000343194	SCV000420992	uncertain significance	Dilated cardiomyopathy 1G	2018-01-13	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	RCV000404036	SCV000420993	uncertain significance	Early-onset myopathy with fatal cardiomyopathy	2018-01-13	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	RCV000298847	SCV000420994	benign	Myopathy, myofibrillar, 9, with early respiratory failure	2018-01-13	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	RCV000393180	SCV000420996	benign	Tibial muscular dystrophy	2018-01-13	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080123	SCV000555613	benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-29	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000082442	SCV000884797	likely benign	not provided	2023-06-28	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000353742	SCV000995524	likely benign	Hypertrophic cardiomyopathy	2017-07-26	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000082442	SCV001152679	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	TTN: BS2
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001170311	SCV001332880	benign	Cardiomyopathy	2018-02-09	criteria provided, single submitter	clinical testing
Genetics and Genomics Program, Sidra Medicine	RCV000353742	SCV001434033	likely benign	Hypertrophic cardiomyopathy		criteria provided, single submitter	research
Genetics and Genomics Program, Sidra Medicine	RCV001293236	SCV001434235	uncertain significance	Primary dilated cardiomyopathy		criteria provided, single submitter	research
Knight Diagnostic Laboratories, Oregon Health and Sciences University	RCV001270084	SCV001448890	likely benign	Short stature; Failure to thrive; Generalized muscle weakness; Delayed speech and language development; Abnormal speech pattern; Abnormality of the immune system; Hypotonia	2019-03-21	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000154897	SCV002572248	likely benign	not specified	2022-08-22	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004529867	SCV004741925	likely benign	TTN-related disorder	2024-02-14	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).