ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.67099T>C (p.Ser22367Pro) (rs72646873)

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Total submissions: 20
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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 RCV000040518 SCV000051644 benign not specified 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000040518 SCV000064209 likely benign not specified 2014-09-05 criteria provided, single submitter clinical testing Ser19799Pro in exon 267 of TTN: This variant is not expected to have clinical si gnificance because it has been identified in 0.2% (15/8182) of European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu /EVS/); there is a lack of conservation across species, including mammals; and i t did not segregate with disease in 1 affected family member from 1 family.
GeneDx RCV000040518 SCV000237450 likely benign not specified 2017-10-03 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 RCV001083546 SCV000286791 likely benign Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-11-28 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000040518 SCV000333058 likely benign not specified 2015-10-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000368971 SCV000422143 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 Clinical Services Laboratory,Illumina RCV000275767 SCV000422144 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 Clinical Services Laboratory,Illumina RCV000333256 SCV000422145 uncertain significance 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 Clinical Services Laboratory,Illumina RCV000260453 SCV000422147 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.
Illumina Clinical Services Laboratory,Illumina RCV000318112 SCV000422148 uncertain significance Myopathy, early-onset, 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.
Ambry Genetics RCV000621791 SCV000735677 likely benign Cardiovascular phenotype 2018-09-13 criteria provided, single submitter clinical testing Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Subpopulation frequency in support of benign classification
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852821 SCV000995550 likely benign Cardiomyopathy; Brugada syndrome 2019-02-16 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000230180 SCV001152797 uncertain significance not provided 2020-06-01 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001170577 SCV001333165 benign Cardiomyopathy 2019-03-26 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000040518 SCV001361796 likely benign not specified 2021-07-27 criteria provided, single submitter clinical testing Variant summary: TTN c.59395T>C (p.Ser19799Pro) results in a non-conservative amino acid change located in the A-band region of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0017 in 247956 control chromosomes, particularly at a frequency of 0.0025 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 4-fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Cardiomyopathy phenotype (0.00063), strongly suggesting that the variant is a benign polymorphism. c.59395T>C has been reported in the literature in individuals affected with hypertrophic cardiomyopathy, sudden unexplained death and atrial fibrillation without strong evidence of causality (e.g. Lopes_2013, Campuzano_2015, Weigl_2019). These reports do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight 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 likely benign.
Athena Diagnostics Inc RCV000040518 SCV001476360 benign not specified 2020-08-27 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000230180 SCV001713224 uncertain significance not provided 2020-07-31 criteria provided, single submitter clinical testing
Clinical Genetics,Academic Medical Center RCV000040518 SCV001922804 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000230180 SCV001927638 likely benign not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000230180 SCV001957102 likely benign not provided no assertion criteria provided clinical testing

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