ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.266C>G (p.Ala89Gly) (rs200165636)

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Total submissions: 15
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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 RCV000172495 SCV000055124 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
GeneDx RCV000172495 SCV000238102 likely benign not provided 2019-09-26 criteria provided, single submitter clinical testing
Invitae RCV000524658 SCV000642890 uncertain significance Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2018-01-12 criteria provided, single submitter clinical testing
Phosphorus, Inc. RCV000578069 SCV000679954 uncertain significance Dilated cardiomyopathy 1G 2017-08-01 criteria provided, single submitter clinical testing
Phosphorus, Inc. RCV000577960 SCV000679955 uncertain significance Limb-girdle muscular dystrophy, type 2J 2017-08-01 criteria provided, single submitter clinical testing
Phosphorus, Inc. RCV000578038 SCV000679956 uncertain significance Tibial muscular dystrophy 2017-08-01 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000172495 SCV001153212 uncertain significance not provided 2018-09-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000577960 SCV001297815 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 RCV000578069 SCV001297816 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 RCV000578038 SCV001303038 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 RCV001142582 SCV001303039 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.
Illumina Clinical Services Laboratory,Illumina RCV001142583 SCV001303040 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.
New York Genome Center RCV001281537 SCV001468846 uncertain significance Brugada syndrome 2019-05-31 criteria provided, single submitter clinical testing The c.266C>G (p.Ala89Gly) variant in the TTN gene substitutes a highly conserved Alanine for Glycine at amino acid 89/35992 (coding exon 3/363). It is identified in gnomAD (39 heterozygotes, 0 homozygotes; allele frequency: 1.379e-4) and ExAC (20 heterozygotes, 0 homozygotes; allele frequency: 1.648e-4). In silico algorithms do not agree on the pathogenicity of this variant, as it is predicted both Deleterious (Provean; score: -2.56) and Tolerated (SIFT; score: 0.441) to the function of the canonical transcript. The Ala89 residue is in the Z-disk of the protein, which is involved in myofibril assembly, stabilization, and maintenance. This variant is reported in ClinVar as a Variant of Uncertain Significance (VarID:192099). The c.266C>G (p.Ala89Gly) variant has been identified in a single individual with hypertrophic cardiomyopathy, however that individual had several additional variants of uncertain significance identified in other cardiomyopathy associated genes [PMID: 30847666]. Given the lack of compelling information regarding the pathogenicity of the c.266C>G (p.Ala89Gly) variant in the TTN gene, it is reported here as a Variant of Uncertain Significance.
Clinical Genetics,Academic Medical Center RCV000172495 SCV001924960 uncertain significance not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000172495 SCV001952708 uncertain significance not provided no assertion criteria provided clinical testing

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