ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.68165A>G (p.Asn22722Ser)

gnomAD frequency: 0.00010  dbSNP: rs200493270
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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, Mass General Brigham Personalized Medicine RCV000216817 SCV000272735 uncertain significance not specified 2015-02-12 criteria provided, single submitter clinical testing The p.Asn20154Ser variant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 15/66666 European chromosomes b y the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs200493270). Computational prediction tools and conservation analysis suggest t hat the p.Asn20154Ser variant may impact the protein. However, none of these too ls are predictive enough to determine pathogenicity. In summary, the clinical si gnificance of the p.Asn20154Ser variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV000537702 SCV000643572 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-11-21 criteria provided, single submitter clinical testing
GeneDx RCV000997415 SCV001816665 likely benign not provided 2018-10-31 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 30847666)
Revvity Omics, Revvity RCV000997415 SCV003822899 uncertain significance not provided 2019-10-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000216817 SCV004804342 likely benign not specified 2024-01-09 criteria provided, single submitter clinical testing Variant summary: TTN c.60461A>G (p.Asn20154Ser) results in a conservative amino acid change located in the A-band region of the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8.5e-05 in 248344 control chromosomes, predominantly at a frequency of 0.00019 within the Non-Finnish European subpopulation in the gnomAD database. However, in certain ethnicities, e.g. in the Swedish, the variant is reported with an even higher frequency (i.e. 0.00046), and this frequency is higher than the estimated maximum expected for a pathogenic variant in TTN causing Dilated Cardiomyopathy (0.00039), suggesting that the variant might be benign. The variant, c.60461A>G, has been reported in the literature in individuals affected with cardiomyopathy (van Lint_2019), however no supportive evidence for causality was provided. 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. ClinVar contains an entry for this variant (Variation ID: 229499). Based on the evidence outlined above, the variant was classified as likely benign.

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