ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.92176C>T (p.Pro30726Ser)

gnomAD frequency: 0.00184  dbSNP: rs72648247
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Total submissions: 25
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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 RCV000082448 SCV000051461 likely benign not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000040789 SCV000064480 likely benign not specified 2015-03-30 criteria provided, single submitter clinical testing p.Pro28158Ser in exon 288 of TTN: This variant is not expected to have clinical significance because it has been identified in 0.5% (77/15570) of South Asian ch romosomes and 0.3% (199/65938) European chromosomes by the Exome Aggregation Con sortium (ExAC, http://exac.broadinstitute.org; dbSNP rs72648247).
GeneDx RCV000082448 SCV000237762 benign not provided 2018-04-24 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 24503780)
Ambry Genetics RCV000247505 SCV000317739 benign Cardiovascular phenotype 2023-05-08 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Eurofins Ntd Llc (ga) RCV000040789 SCV000333503 likely benign not specified 2015-07-31 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000277773 SCV000420859 uncertain significance Hypertrophic cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000330728 SCV000420860 uncertain significance Dilated Cardiomyopathy, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000387528 SCV000420861 uncertain significance Limb-Girdle Muscular Dystrophy, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000290790 SCV000420862 uncertain significance Early-onset myopathy with fatal cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000348133 SCV000420863 uncertain significance Tibial muscular dystrophy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000380748 SCV000420864 uncertain significance Myopathy, myofibrillar, 9, with early respiratory failure 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV001083918 SCV000555653 benign Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2024-01-29 criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego RCV000852789 SCV000995515 likely benign Supraventricular tachycardia 2017-10-02 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000082448 SCV001152662 likely benign not provided 2023-11-01 criteria provided, single submitter clinical testing TTN: BS2
Illumina Laboratory Services, Illumina RCV001132527 SCV001292190 uncertain significance Autosomal recessive 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 Laboratory Services, Illumina RCV001132528 SCV001292192 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000040789 SCV001362767 benign not specified 2020-12-04 criteria provided, single submitter clinical testing Variant summary: TTN c.84472C>T (p.Pro28158Ser) results in a non-conservative amino acid change located in the A-band of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0027 in 245714 control chromosomes in the gnomAD database, including 3 homozygotes. The observed variant frequency 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 benign. Co-occurrences with a pathogenic variant has been reported (MYBPC3 c.3628-41_3628-17del25), providing supporting evidence for a benign role. Eight 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 (benign/likely benign n=6, VUS n=2). Based on the evidence outlined above, the variant was classified as benign.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001798198 SCV002043060 benign Cardiomyopathy 2019-10-28 criteria provided, single submitter clinical testing
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine RCV000290790 SCV004175766 likely benign Early-onset myopathy with fatal cardiomyopathy 2023-03-01 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000082448 SCV001744097 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000040789 SCV001922154 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000040789 SCV001931831 benign not specified no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000040789 SCV001954515 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000082448 SCV001971338 likely benign not provided no assertion criteria provided clinical testing
Practice for Gait Abnormalities, David Pomarino, Competency Network Toe Walking c/o Practice Pomarino RCV002227930 SCV002507269 likely pathogenic Tip-toe gait no assertion criteria provided clinical testing

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