ClinVar Miner

Submissions for variant NM_133379.5(TTN):c.12724A>G (p.Ser4242Gly)

gnomAD frequency: 0.00015  dbSNP: rs541264551
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Total submissions: 3
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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 RCV000152452 SCV000201546 benign not specified 2018-09-11 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV003114301 SCV003799731 uncertain significance not provided 2022-05-06 criteria provided, single submitter clinical testing The TTN c.12724A>G; p.Ser4242Gly variant (rs541264551; ClinVar Variation ID: 166268) is rare in the general population (<0.2% allele frequency in the Genome Aggregation Database) and has not been reported in the medical literature in association with dilated cardiomyopathy (DCM) or other TTN-related disease. The clinical relevance of rare missense variants in this gene, which are identified on average once per individual sequenced in affected populations (Herman 2012), is not well understood. Yet, evidence suggests that the vast majority of such missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Thus, the clinical significance of the p.Ser4242Gly variant cannot be determined with certainty. Begay RL et al. Role of Titin Missense Variants in Dilated Cardiomyopathy. J Am Heart Assoc. 2015 Nov 13;4(11). PMID: 26567375. Herman DS et al. Truncations of titin causing dilated cardiomyopathy. N Engl J Med. 2012 Feb 16;366(7):619-28. PMID: 22335739.
PreventionGenetics, part of Exact Sciences RCV004532705 SCV004120177 uncertain significance TTN-related disorder 2023-05-25 criteria provided, single submitter clinical testing The TTN c.12724A>G variant is predicted to result in the amino acid substitution p.Ser4242Gly. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.14% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-179614403-T-C). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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