ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.68437G>A (p.Glu22813Lys) (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, Partners HealthCare 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 RCV000154926 SCV000236779 likely benign not specified 2018-01-22 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 RCV000234385 SCV000286798 uncertain significance Dilated cardiomyopathy 1G; 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 Insufficient or inconclusive evidence
Illumina Clinical Services Laboratory,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 Clinical Services Laboratory,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 Clinical Services Laboratory,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 Clinical Services Laboratory,Illumina RCV000375502 SCV000422086 uncertain significance 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 Clinical Services Laboratory,Illumina RCV000262197 SCV000422087 uncertain significance Myopathy, early-onset, 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.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000154926 SCV000701002 benign not specified 2017-01-03 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000172272 SCV001152791 uncertain significance not provided 2018-07-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000154926 SCV001362823 uncertain significance not specified 2019-10-07 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 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. 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 clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (two classified it as a VUS, two as likely benign, and one as benign). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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