ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.31757C>A (p.Pro10586Gln) (rs200459347)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 14
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000040123 SCV000063814 uncertain significance not specified 2015-04-18 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Pro9342Gln in TTN has been previously identified by our laboratory in 1 Caucasian infant with DCM and 1 Black adult with HCM. This variant has also been identified in 0.16% (16/9754) of African chromosomes by the Exome Aggregation Consortium (ExAC, http ://exac.broadinstitute.org; dbSNP rs200459347). Computational prediction tools a nd conservation analysis suggest that this variant may not impact the protein, t hough this information is not predictive enough to rule out pathogenicity. In su mmary, while the clinical significance of the p.Pro9342Gln variant is uncertain, its frequency suggests that it is more likely to be benign.
GeneDx RCV000725032 SCV000237069 likely benign not provided 2020-11-27 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 24503780, 27930701)
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000725032 SCV000333370 uncertain significance not provided 2015-07-21 criteria provided, single submitter clinical testing
Invitae RCV001085078 SCV000555001 likely benign Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-11-15 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000725032 SCV001152993 uncertain significance not provided 2019-04-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001131660 SCV001291291 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 RCV001131661 SCV001291292 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.
Illumina Clinical Services Laboratory,Illumina RCV001131662 SCV001291293 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 RCV001131663 SCV001291294 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 RCV001131664 SCV001291295 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.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001170626 SCV001333217 benign Cardiomyopathy 2018-01-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000040123 SCV001437321 benign not specified 2020-09-25 criteria provided, single submitter clinical testing Variant summary: TTN c.28025C>A (p.Pro9342Gln) results in a non-conservative amino acid change located in the I band region (https://www.cardiodb.org/titin/) of the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00049 in 247940 control chromosomes, predominantly at a frequency of 0.0017 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 4 fold of 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 African or African-American origin. c.28025C>A has been reported in the literature in individuals affected with Sudden Infant Death Syndrome, Sudden Unexplained Death and Dilated Cardiomyopathy (Sanchez_2016, Pugh_2014, Campuzano_2015) without strong evidence of causality. These reports therefore, do 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. Eight ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign (n=4) or uncertain significance (n=4). Based on the evidence outlined above, the variant was classified as benign.
Clinical Genetics,Academic Medical Center RCV000040123 SCV001918680 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000725032 SCV001952644 likely benign not provided no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.