ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.40498G>T (p.Val13500Phe)

gnomAD frequency: 0.00066  dbSNP: rs201944202
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Total submissions: 22
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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 RCV000082399 SCV000055005 likely benign not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000040205 SCV000063896 likely benign not specified 2018-11-26 criteria provided, single submitter clinical testing The p.Val10932Phe variant in TTN is classified as likely benign because it has b een identified in 0.1% (132/111288) of European chromosomes by gnomAD (http://gn omad.broadinstitute.org). ACMG/AMP Criteria applied: BS1.
GeneDx RCV000082399 SCV000237141 likely benign not provided 2020-12-04 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 23861362)
Invitae RCV001086509 SCV000261466 likely benign Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2024-01-31 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000082399 SCV000335991 uncertain significance not provided 2016-01-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000385921 SCV000423463 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 Laboratory Services, Illumina RCV000294379 SCV000423464 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 Laboratory Services, Illumina RCV000337656 SCV000423465 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 Laboratory Services, Illumina RCV000279186 SCV000423467 uncertain significance Early-onset myopathy 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.
Illumina Laboratory Services, Illumina RCV000336318 SCV000423468 uncertain significance Autosomal recessive 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.
Athena Diagnostics Inc RCV000082399 SCV000616072 likely benign not provided 2018-05-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV000620121 SCV000735573 likely benign Cardiovascular phenotype 2018-07-10 criteria provided, single submitter clinical testing This alteration is classified as likely 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.
CeGaT Center for Human Genetics Tuebingen RCV000082399 SCV001152930 uncertain significance not provided 2019-06-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000082399 SCV001159795 uncertain significance not provided 2020-05-05 criteria provided, single submitter clinical testing The TTN c.32794G>T; p.Val10932Phe variant is rare in the general population (<1% allele frequency in the Genome Aggregation Database) and has not been reported in the medical literature in association with dilated cardiomyopathy (DCM) or other TTN-related disease. The clinical relevance of rare missense variants in this gene, which are identified on average once per individual sequenced in affected populations (Herman 2012), is not well understood. Yet, evidence suggests that the vast majority of such missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Thus, the clinical significance of the p.Val10932Phe variant cannot be determined with certainty. References: Begay RL et al. Role of Titin Missense Variants in Dilated Cardiomyopathy. J Am Heart Assoc. 2015 Nov 13;4(11). Herman DS et al. Truncations of titin causing dilated cardiomyopathy. N Engl J Med. 2012 Feb 16;366(7):619-28.
Mayo Clinic Laboratories, Mayo Clinic RCV000082399 SCV001714052 uncertain significance not provided 2023-05-26 criteria provided, single submitter clinical testing BP4
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001798149 SCV002042464 benign Cardiomyopathy 2019-08-09 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000040205 SCV002511923 likely benign not specified 2022-04-09 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000082399 SCV001744391 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000082399 SCV001921411 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000082399 SCV001928675 likely benign not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000082399 SCV001956523 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000082399 SCV001964352 likely benign not provided no assertion criteria provided clinical testing

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