ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.102811G>A (p.Val34271Ile)

dbSNP: rs794727542
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000724604 SCV000229376 uncertain significance not provided 2015-02-13 criteria provided, single submitter clinical testing
GeneDx RCV000259176 SCV000237906 uncertain significance not specified 2014-03-18 criteria provided, single submitter clinical testing Missense variants in the TTN gene are considered 'unclassified' if they are not previously reported in the literature and do not have >1% frequency in the population to be considered a polymorphism. Research indicates that truncating mutations in the TTN gene are expected to account for approximately 25% of familial and 18% of sporadic idiopathic DCM; however, truncating variants in the TTN gene have been reported in approximately 3% of reported control alleles. There has been little investigation into non-truncating variants. (Herman D et al. Truncations of titin causing dilated cardiomyopathy. N Eng J Med 366:619-628, 2012) The variant is found in CARDIOMYOPATHY panel(s).
Invitae RCV000818971 SCV000959610 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2019-01-26 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 34271 of the TTN protein (p.Val34271Ile).  There is a small physicochemical difference between valine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TTN-related disease. ClinVar contains an entry for this variant (Variation ID: 196653). This variant is located in the M band of TTN (PMID: 25589632). Variants in this region may be relevant for neuromuscular disorders, but have not been definitively shown to cause cardiomyopathy (PMID: 23975875). Algorithms developed to predict the effect of missense changes on protein structure and function are unavailable for the TTN gene. The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego RCV000852774 SCV000995496 likely benign Cardiomyopathy 2017-03-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV002390431 SCV002670887 uncertain significance Cardiovascular phenotype 2019-12-23 criteria provided, single submitter clinical testing The p.V25206I variant (also known as c.75616G>A), located in coding exon 185 of the TTN gene, results from a G to A substitution at nucleotide position 75616. The valine at codon 25206 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and isoleucine is the reference amino acid in other 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.
Revvity Omics, Revvity Omics RCV000724604 SCV003825509 uncertain significance not provided 2022-01-11 criteria provided, single submitter clinical testing

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