ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.14698G>A (p.Ala4900Thr) (rs72648923)

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Total submissions: 17
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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 RCV000172701 SCV000051451 likely benign not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000039861 SCV000063552 benign not specified 2013-01-30 criteria provided, single submitter clinical testing Ala3656Thr in exon 47 of TTN: This variant is not expected to have clinical sign ificance because it has been identified in 0.3% (27/8226) of European American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS), as well as in 3.2% (6/186) of Finnish chromosomes f rom a broad population by the 1000 Genomes Project (dbSNP rs72648923).
PreventionGenetics,PreventionGenetics RCV000039861 SCV000315400 benign not specified criteria provided, single submitter clinical testing
Ambry Genetics RCV000247436 SCV000318618 benign Cardiovascular phenotype 2013-05-02 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000039861 SCV000336584 benign not specified 2015-10-15 criteria provided, single submitter clinical testing
Invitae RCV001084081 SCV000555382 benign Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-11-28 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769086 SCV000900459 benign Cardiomyopathy 2017-08-11 criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852917 SCV000995659 benign Long QT syndrome 2017-10-25 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000172701 SCV001153090 uncertain significance not provided 2016-05-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283480 SCV001159140 benign none provided 2020-02-20 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001129220 SCV001288728 benign Myopathy, myofibrillar, 9, with early respiratory failure 2017-08-16 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 RCV001129221 SCV001288729 benign Limb-girdle muscular dystrophy, type 2J 2017-08-16 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 RCV001129222 SCV001288730 benign Myopathy, early-onset, with fatal cardiomyopathy 2017-08-16 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 RCV001129223 SCV001288731 benign Tibial muscular dystrophy 2017-08-16 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 RCV001129224 SCV001288732 benign Dilated cardiomyopathy 1G 2017-08-16 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000039861 SCV001432112 benign not specified 2020-08-17 criteria provided, single submitter clinical testing Variant summary: TTN c.10966G>A (p.Ala3656Thr) results in a non-conservative amino acid change located in the I-band 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 0.0034 in 248448 control chromosomes in the gnomAD database, including 2 homozygotes. The observed variant frequency is approximately 9 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 benign. To our knowledge, no occurrence of c.10966G>A in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (benign n=6, VUS n=1). Based on the evidence outlined above, the variant was classified as benign.
GeneDx RCV000172701 SCV000238204 not provided not provided 2014-08-27 no assertion provided clinical testing Missense variants in the TTN gene are considered 'unclassified' if they are not previously reported in the literature and do not have >1% frequency in the population to be considered a polymorphism. Research indicates that truncating mutations in the TTN gene are expected to account for approximately 25% of familial and 18% of sporadic idiopathic DCM; however, truncating variants in the TTN gene have been reported in approximately 3% of reported control alleles. There has been little investigation into non-truncating variants. (Herman D et al. Truncations of titin causing dilated cardiomyopathy. N Eng J Med 366:619-628, 2012) The variant is found in DCM,DCM-CRDM,CARDIOMYOPATHY panel(s).

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