ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.62681G>T (p.Cys20894Phe)

gnomAD frequency: 0.00013  dbSNP: rs370080086
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mayo Clinic Laboratories, Mayo Clinic RCV000997433 SCV001713234 uncertain significance not provided 2020-02-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV002454246 SCV002617305 uncertain significance Cardiovascular phenotype 2018-12-31 criteria provided, single submitter clinical testing The p.C11829F variant (also known as c.35486G>T), located in coding exon 131 of the TTN gene, results from a G to T substitution at nucleotide position 35486. The cysteine at codon 11829 is replaced by phenylalanine, an amino acid with highly dissimilar properties. 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.
Fulgent Genetics, Fulgent Genetics RCV002489499 SCV002777234 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 2021-08-03 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000997433 SCV003824839 uncertain significance not provided 2022-06-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003317410 SCV004020324 uncertain significance not specified 2023-06-19 criteria provided, single submitter clinical testing Variant summary: TTN c.54977G>T (p.Cys18326Phe) results in a non-conservative amino acid change located in the A-band domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.6e-05 in 244556 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in TTN causing Dilated Cardiomyopathy (8.6e-05 vs 0.00039), allowing no conclusion about variant significance. c.54977G>T has been reported in the literature in at least one individual affected with Dilated Cardiomyopathy (example: Mazzarotto_2020) and as a VUS in at least one individual affected with left ventricular noncompaction and hypertrophic cardiomyopathy (example: Mehaney_2022). 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 publications have been ascertained in the context of this evaluation (PMID: 31983221, 34036930). 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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