ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.101665G>A (p.Val33889Ile) (rs34924609)

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Total submissions: 19
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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 RCV000040908 SCV000054869 benign not specified 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000040908 SCV000064599 likely benign not specified 2017-08-25 criteria provided, single submitter clinical testing p.Val31321Ile in exon 307 of TTN: This variant is not expected to have clinical significance because it has been identified in 0.6% (762/126186) of European ch romosomes including 2 homozygotes by the Genome Aggregation Database (gnomAD, ht tp://gnomad.broadinstitute.org; dbSNP rs34924609).
Genetic Services Laboratory,University of Chicago RCV000040908 SCV000153422 likely benign not specified 2017-02-02 criteria provided, single submitter clinical testing
GeneDx RCV000040908 SCV000169460 benign not specified 2013-11-07 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 RCV001079468 SCV000262071 benign Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2019-12-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000040908 SCV000315626 likely benign not specified criteria provided, single submitter clinical testing
Ambry Genetics RCV000246329 SCV000318174 likely benign Cardiovascular phenotype 2013-09-24 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000040908 SCV000332314 benign not specified 2015-06-23 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000713950 SCV000844599 benign not provided 2019-07-31 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769857 SCV000901283 likely benign Cardiomyopathy 2017-05-11 criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852780 SCV000995503 benign Hypertrophic cardiomyopathy; Supraventricular tachycardia 2019-03-25 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000713950 SCV001152598 likely benign not provided 2020-02-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000040908 SCV001159543 benign not specified 2019-02-27 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001131492 SCV001291119 uncertain significance Limb-girdle muscular dystrophy, type 2J 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001131493 SCV001291120 benign Tibial muscular dystrophy 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV001131494 SCV001291121 benign Myopathy, myofibrillar, 9, with early respiratory failure 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV001131495 SCV001291122 likely benign Dilated cardiomyopathy 1G 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV001134484 SCV001294231 uncertain significance Myopathy, early-onset, with fatal cardiomyopathy 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Integrated Genetics/Laboratory Corporation of America RCV000040908 SCV001361307 benign not specified 2020-08-31 criteria provided, single submitter clinical testing Variant summary: TTN c.93961G>A (p.Val31321Ile) results in a conservative amino acid change located in the M-band region of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0031 in 247810 control chromosomes, predominantly at a frequency of 0.006 within the Non-Finnish European subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database 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 a benign polymorphism found primarily in populations of Non-Finnish European origin. c.93961G>A has been reported in the literature in individuals affected with Cardiomyopathy and Sudden Unexplained Death (e.g. Pugh_2014, Campuzano_2015). These reports do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. A co-occurrence with a pathogenic variant has been reported (PKP2 c.2146-1G>C; Internal testing). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Nine ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign. An additional ClinVar submitter (evaluation after 2014) cites the variant under different accessions with varying classifications (benign, likely benign and uncertain significance). Based on the evidence outlined above, the variant was classified as benign.

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