ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.70975G>A (p.Gly23659Ser)

gnomAD frequency: 0.00006  dbSNP: rs376256345
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000280725 SCV000332851 uncertain significance not provided 2015-07-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000811215 SCV000951471 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2018-07-03 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 23659 of the TTN protein (p.Gly23659Ser). There is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs376256345, ExAC 0.009%). This variant (also known as G21091S in the literature) has been reported in an individual affected with juvenile sudden cardiac death (PMID: 25447171). ClinVar contains an entry for this variant (Variation ID: 281841). 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 missense changes on protein structure and function are unavailable for the TTN gene. In summary, this variant is a rare missense change with unknown impact on protein function. Missense variants in this region of the TTN gene are typically not causative for cardiac disease, but may be relevant for neuromuscular disorders. However, the available evidence is currently insufficient to determine this variant’s role in disease. Therefore, it has been classified as a Variant of Uncertain Significance
Athena Diagnostics RCV000280725 SCV001146479 uncertain significance not provided 2018-10-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV002328758 SCV002632999 uncertain significance Cardiovascular phenotype 2018-12-05 criteria provided, single submitter clinical testing The p.G14594S variant (also known as c.43780G>A), located in coding exon 153 of the TTN gene, results from a G to A substitution at nucleotide position 43780. The glycine at codon 14594 is replaced by serine, an amino acid with similar properties. This alteration was reported (as NM_133378.4:c.63271G>A p.G21091S) in a sudden unexplained death case; however, clinical details were not provided and an additional cardiac variant was also detected (Campuzano O et al. Forensic Sci. Int., 2014 12;245:30-7). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV000280725 SCV003821783 uncertain significance not provided 2021-12-17 criteria provided, single submitter clinical testing

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