ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.88183T>C (p.Phe29395Leu)

gnomAD frequency: 0.00010  dbSNP: rs55940667
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000172214 SCV000051117 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000040743 SCV000064434 uncertain significance not specified 2012-10-17 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Phe26827Leu var iant in TTN has not been reported in the literature nor previously identified by our laboratory. It has been identified in 1/194 Han Chinese chromosomes from a broad population by the 1000 Genomes project (dbSNP rs55940667). Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein , though dolphin carries a leucine (Leu; this variant) despite high amino acid c onservation nearby, suggesting that this variant may be tolerated. This variant is more likely benign but at this time, additional information is needed to full y assess its clinical significance.
GeneDx RCV000040743 SCV000237694 uncertain significance not specified 2014-07-08 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).
Ambry Genetics RCV000245043 SCV000319087 uncertain significance Cardiovascular phenotype 2013-09-23 criteria provided, single submitter clinical testing The p.F26827L variant (also known as c.80479T>C) is located in coding exon 278 of the TTNgene. This alteration results from a T to C substitution at nucleotide position 80479. The phenylalanine at codon 26827 is replaced by leucine, an amino acid with highly similar properties.This variant was previously reported in the SNPDatabase as rs55940667. Based on data from the 1000 Genomes Project, the C-allele has an overall frequency of approximately 0.05% (1/2184). The highest observed frequency was 0.52% (1/194) Han Chinese chromosomes studied. This amino acid position is not conserved on sequence alignment. This variant is predicted to be benign by PolyPhen in silico analyses. Since supporting evidence is limited at this time, the clinical significance of p.F26827L remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001086668 SCV000765026 likely benign Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2025-01-06 criteria provided, single submitter clinical testing

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