ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.43577G>A (p.Arg14526Gln)

gnomAD frequency: 0.00018  dbSNP: rs373491468
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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Mass General Brigham Personalized Medicine RCV000040239 SCV000063930 uncertain significance not specified 2013-01-02 criteria provided, single submitter clinical testing The Arg11958Gln variant in TTN has not been reported in the literature nor previ ously identified by our laboratory. This variant has been identified in 3/8288 E uropean American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS/). Arginine (Arg) at position 11958 is poorly conserved in evolution, and 1 species (zebrafish) carries the variant amino acid (Gln) at this position, suggesting this change may be tolerated. Com putational analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, an d SIFT) suggest that the Arg11958Gln variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. Additional information is needed to fully assess the clinical significance of the Arg11958G ln variant.
Eurofins NTD LLC (GA) RCV000724718 SCV000226857 uncertain significance not provided 2015-04-11 criteria provided, single submitter clinical testing
GeneDx RCV000724718 SCV000237167 likely benign not provided 2019-06-14 criteria provided, single submitter clinical testing
Invitae RCV000473565 SCV000542559 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2016-04-29 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000724718 SCV000616082 uncertain significance not provided 2020-09-21 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV001133884 SCV001293598 uncertain significance Autosomal recessive 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 Laboratory Services,Illumina RCV001135394 SCV001295171 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 Laboratory Services,Illumina RCV001135395 SCV001295172 uncertain significance Early-onset myopathy 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 Laboratory Services,Illumina RCV001135396 SCV001295173 benign Tibial muscular dystrophy 2017-06-01 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 Laboratory Services,Illumina RCV001135397 SCV001295174 benign Myopathy, myofibrillar, 9, with early respiratory failure 2017-06-01 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 RCV000040239 SCV001519475 uncertain significance not specified 2021-03-15 criteria provided, single submitter clinical testing Variant summary: TTN c.35873G>A (p.Arg11958Gln) results in a conservative amino acid change located in the I-band region (cardiodb.org) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 9.7e-05 in 238322 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in TTN causing Dilated Cardiomyopathy (9.7e-05 vs 0.00039), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.35873G>A in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Six other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, citing the variant as benign/likely benign (n=2) and uncertain significance (n=4). Based on the evidence outlined above, the variant was classified as uncertain significance.
Clinical Genetics, Academic Medical Center RCV000724718 SCV001918312 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000724718 SCV001975599 likely benign not provided no assertion criteria provided clinical testing

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