ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.25853G>A (p.Gly8618Glu)

gnomAD frequency: 0.00007  dbSNP: rs369947439
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000725269 SCV000238367 likely benign not provided 2021-06-08 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 30086531)
Eurofins Ntd Llc (ga) RCV000725269 SCV000335511 uncertain significance not provided 2015-09-22 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000461658 SCV000543127 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2016-08-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003323436 SCV004029902 uncertain significance not specified 2023-07-05 criteria provided, single submitter clinical testing Variant summary: TTN c.22121G>A (p.Gly7374Glu) results in a non-conservative amino acid change located in the I-band of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.4e-05 in 248596 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in TTN causing Dilated Cardiomyopathy (4.4e-05 vs 0.00039), allowing no conclusion about variant significance. c.22121G>A has been reported in the literature in an individual affected with sudden cardiac death without evidence of causality (Campuzano_2018). 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. The following publication has been ascertained in the context of this evaluation (PMID: 30086531). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014, and classified it as uncertain significance (n=2) or likely benign (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.

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