ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.835C>T (p.Arg279Trp) (rs138060032)

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Total submissions: 14
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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 RCV000172493 SCV000051348 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000219791 SCV000272796 likely benign not specified 2018-04-09 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
Invitae RCV000468349 SCV000542790 uncertain significance Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2017-05-08 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000172493 SCV000609012 uncertain significance not provided 2017-04-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000617531 SCV000735597 uncertain significance Cardiovascular phenotype 2018-11-13 criteria provided, single submitter clinical testing The p.R279W variant (also known as c.835C>T), located in coding exon 5 of the TTN gene, results from a C to T substitution at nucleotide position 835. The arginine at codon 279 is replaced by tryptophan, an amino acid with dissimilar properties. This variant was reported in cis with a truncating TTN alteration in a family with both dilated cardiomyopathy and peripartum cardiomyopathy (van Spaendonck-Zwarts KY et al. Eur Heart J. 2014;35:2165-73). This alteration has also been reported as a secondary cardiac variant in an exome cohort, and was detected in a sudden unexplained death case with variants in other cardiac-related genes (Ng D et al. Circ Cardiovasc Genet. 2013;6:337-46; Sanchez O et al. PLoS ONE. 2016;11(12):e0167358). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769143 SCV000900517 uncertain significance Cardiomyopathy 2019-02-11 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000172493 SCV001146514 uncertain significance not provided 2018-09-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001131435 SCV001291056 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.
Illumina Clinical Services Laboratory,Illumina RCV001134416 SCV001294155 uncertain significance 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 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 RCV001134417 SCV001294156 uncertain significance 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 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 RCV001134418 SCV001294157 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 RCV000013495 SCV001294158 uncertain significance 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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
OMIM RCV000013495 SCV000033742 pathogenic Myopathy, myofibrillar, 9, with early respiratory failure 2005-06-10 no assertion criteria provided literature only
GeneDx RCV000172493 SCV000238291 not provided not provided 2014-09-04 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 CARDIOMYOPATHY panel(s).

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