ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.60734G>A (p.Arg20245Gln)

gnomAD frequency: 0.00016  dbSNP: rs575837567
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000231887 SCV000286760 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2016-10-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 20245 of the TTN protein (p.Arg20245Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs575837567, ExAC 0.02%) but has not been reported in the literature. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Eurofins Ntd Llc (ga) RCV000313555 SCV000333527 uncertain significance not provided 2017-01-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV002321866 SCV002607143 uncertain significance Cardiovascular phenotype 2019-03-26 criteria provided, single submitter clinical testing The p.R11180Q variant (also known as c.33539G>A), located in coding exon 131 of the TTN gene, results from a G to A substitution at nucleotide position 33539. The arginine at codon 11180 is replaced by glutamine, an amino acid with highly similar properties. This variant was identified in a population-based cohort study of QT interval variation; however clinical details were not provided (Kapoor A et al. Sci Rep, 2016;6:28356 (reported as p.R20245Q)). This amino acid position is highly 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.
Revvity Omics, Revvity Omics RCV000313555 SCV003819706 uncertain significance not provided 2020-01-24 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003488484 SCV004241828 uncertain significance not specified 2023-12-04 criteria provided, single submitter clinical testing Variant summary: TTN c.53030G>A (p.Arg17677Gln) results in a conservative amino acid change located in the A band region of the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.8e-05 in 247704 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in TTN causing Dilated Cardiomyopathy (4.8e-05 vs 0.00039), allowing no conclusion about variant significance. c.53030G>A has been reported in the literature in a population-based cohort study of QT interval variation; however clinical details were not providedy (Kapoor_2016). These report(s) do not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 27321809). Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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