ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.104204C>T (p.Thr34735Met)

gnomAD frequency: 0.00004  dbSNP: rs755986938
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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) RCV000390855 SCV000345013 uncertain significance not provided 2016-09-22 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001850468 SCV002151934 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2024-07-08 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 34735 of the TTN protein (p.Thr34735Met). This variant is present in population databases (rs755986938, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 290453). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant is located in the M band of TTN (PMID: 25589632). Non-truncating variants in this region may be relevant for neuromuscular disorders, but have not been definitively shown to cause cardiomyopathy (PMID: 23975875). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002402005 SCV002669547 uncertain significance Cardiovascular phenotype 2019-11-13 criteria provided, single submitter clinical testing The p.T25670M variant (also known as c.77009C>T), located in coding exon 185 of the TTN gene, results from a C to T substitution at nucleotide position 77009. The threonine at codon 25670 is replaced by methionine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002504021 SCV002815325 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9 2021-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000390855 SCV005328203 uncertain significance not provided 2024-03-15 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Missense variant in a gene in which most reported pathogenic variants are truncating/loss-of-function; Has not been previously published as pathogenic or benign to our knowledge

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