ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.87878G>A (p.Arg29293His) (rs202001776)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000154903 SCV000204585 uncertain significance not specified 2013-12-06 criteria provided, single submitter clinical testing The Arg26725His variant in TTN has not been reported in individuals with cardiom yopathy but has been identified in 2/3934 African American chromosomes by the NH LBI Exome Sequencing Project (; dbSNP rs2020017 76). Computational analyses (biochemical amino acid properties, conservation, Al ignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an im pact to the protein. Additional information is needed to fully assess the clinic al significance of the Arg26725His variant.
Ambry Genetics RCV000622203 SCV000736553 likely benign Cardiovascular phenotype 2020-09-11 criteria provided, single submitter clinical testing Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;In silico models in agreement (benign);Other strong data supporting benign classification
Invitae RCV000643154 SCV000764841 uncertain significance Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2017-12-08 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000727801 SCV000855213 uncertain significance not provided 2018-03-27 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000154903 SCV001442584 uncertain significance not specified 2020-10-26 criteria provided, single submitter clinical testing Variant summary: TTN c.80174G>A (p.Arg26725His) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5.2e-05 in 248862 control chromosomes in the gnomAD database, including 1 homozygotes. This frequency is not significantly higher than expected for a pathogenic variant in TTN causing Dilated Cardiomyopathy (5.2e-05 vs 0.00039), allowing no conclusion about variant significance. c.80174G>A has been reported in the literature in one individual affected with sudden death (Campuzano_2015). This report does not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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