ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.74602A>G (p.Ile24868Val) (rs72646898)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000330878 SCV000421813 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 Clinical Services Laboratory,Illumina RCV000369107 SCV000421814 uncertain significance Myopathy, early-onset, 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 Clinical Services Laboratory,Illumina RCV000276928 SCV000421815 uncertain significance 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 Clinical Services Laboratory,Illumina RCV000325387 SCV000421816 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 Clinical Services Laboratory,Illumina RCV000382277 SCV000421817 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.
Invitae RCV000469841 SCV000542387 uncertain significance Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2017-11-16 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000512928 SCV000608996 uncertain significance not provided 2021-06-01 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000512928 SCV000701537 uncertain significance not provided 2018-04-23 criteria provided, single submitter clinical testing
GeneDx RCV000512928 SCV000970574 likely benign not provided 2021-04-29 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001280555 SCV001467751 likely benign not specified 2020-12-29 criteria provided, single submitter clinical testing Variant summary: TTN c.66898A>G (p.Ile22300Val) results in a conservative amino acid change located in the A-band region of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00023 in 247298 control chromosomes, predominantly at a frequency of 0.00045 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately equal to the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Dilated Cardiomyopathy phenotype (0.00039), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. c.66898A>G has been reported in the literature in a European individual affected with Arrhythmogenic Right Ventricular Cardiomyopathy (Campuzano_2015). This report does not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance and two ClinVar submitters (evaluation after 2014) cite it as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Mayo Clinic Laboratories, Mayo Clinic RCV000512928 SCV001714032 uncertain significance not provided 2020-04-22 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000512928 SCV001743159 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000512928 SCV001917388 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000512928 SCV001931378 likely benign not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000512928 SCV001957852 likely benign not provided no assertion criteria provided clinical testing

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