ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.68437G>A (p.Glu22813Lys)

gnomAD frequency: 0.00019  dbSNP: rs200797552
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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000172272 SCV000051268 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000154926 SCV000204608 likely benign not specified 2017-12-06 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
GeneDx RCV000172272 SCV000236779 likely benign not provided 2020-10-01 criteria provided, single submitter clinical testing
Invitae RCV000234385 SCV000286798 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV000248442 SCV000318037 uncertain significance Cardiovascular phenotype 2013-01-06 criteria provided, single submitter clinical testing There is insufficient or conflicting evidence for classification of this alteration.
Illumina Laboratory Services, Illumina RCV000370118 SCV000422083 benign Myopathy, myofibrillar, 9, with early respiratory failure 2017-11-07 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 RCV000261085 SCV000422084 benign Tibial muscular dystrophy 2017-11-07 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 RCV000316255 SCV000422085 likely benign Dilated cardiomyopathy 1G 2017-11-07 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 determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina RCV000375502 SCV000422086 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-11-07 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 RCV000262197 SCV000422087 uncertain significance Early-onset myopathy with fatal cardiomyopathy 2017-11-07 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.
Eurofins Ntd Llc (ga) RCV000154926 SCV000701002 benign not specified 2017-01-03 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000172272 SCV001152791 likely benign not provided 2023-11-01 criteria provided, single submitter clinical testing TTN: BS1
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000154926 SCV001362823 uncertain significance not specified 2021-10-11 criteria provided, single submitter clinical testing Variant summary: TTN c.60733G>A (p.Glu20245Lys) results in a conservative amino acid change located in the A-Band region of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00033 in 248116 control chromosomes, predominantly at a frequency of 0.0075 within the Ashkenazi Jewish subpopulation in the gnomAD database. This frequency is about 12 times higher than expected for a pathogenic variant in TTN causing Cardiomyopathy (0.0075 vs 0.00063), suggesting a benign role for the variant of interest. To our knowledge, no occurrence of c.60733G>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Five ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign and three ClinVar submitters (evaluation after 2014) cite it as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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