ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.81558T>C (p.Asn27186=) (rs56181243)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000040669 SCV000064360 benign not specified 2012-07-18 criteria provided, single submitter clinical testing Asn24618Asn in Exon 275 of TTN: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence and has been identified in 0.6% (43/6678) of Eur opean American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs56181243).
GeneDx RCV000040669 SCV000169382 benign not specified 2013-12-09 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.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000040669 SCV000228502 benign not specified 2014-11-14 criteria provided, single submitter clinical testing
Invitae RCV001083853 SCV000286855 benign Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2019-12-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000040669 SCV000315568 benign not specified criteria provided, single submitter clinical testing
Ambry Genetics RCV000243142 SCV000318236 likely benign Cardiovascular phenotype 2012-07-13 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000343025 SCV000421447 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 RCV000401208 SCV000421448 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 RCV000289639 SCV000421449 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 RCV000392160 SCV000421451 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 RCV000311788 SCV000421452 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000040669 SCV000884765 benign not specified 2018-09-28 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768912 SCV000900285 benign Cardiomyopathy 2015-12-08 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000756835 SCV001152720 uncertain significance not provided 2017-10-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000040669 SCV001363888 benign not specified 2019-10-30 criteria provided, single submitter clinical testing Variant summary: TTN c.73854T>C alters a non-conserved nucleotide resulting in a synonymous change. 3/3 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0062 in 248042 control chromosomes in the gnomAD database, including 11 homozygotes. The observed variant frequency is approximately 10 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 benign. To our knowledge, no occurrence of c.73854T>C in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.

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