ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.65727C>T (p.Gly21909=)

gnomAD frequency: 0.00001  dbSNP: rs1246746665
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000548580 SCV000643533 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2018-03-21 criteria provided, single submitter clinical testing This sequence change affects codon 21909 of the TTN mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the TTN protein. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TTN-related disease. ClinVar contains an entry for this variant (Variation ID: 467382). This variant identified in the TTN gene is located in the A band of the resulting protein (PMID: 25589632). It is unclear how this variant impacts the function of this protein. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a novel silent change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV003159836 SCV003858689 uncertain significance Cardiovascular phenotype 2023-02-10 criteria provided, single submitter clinical testing The c.38532C>T variant (also known as p.G12844G), located in coding exon 140 of the TTN gene, results from a C to T substitution at nucleotide position 38532. This nucleotide substitution does not change the glycine at codon 12844. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004735607 SCV005366945 likely benign TTN-related disorder 2024-04-11 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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