ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.95415C>A (p.Phe31805Leu)

gnomAD frequency: 0.00002  dbSNP: rs587780983
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001813757 SCV000169430 uncertain significance not provided 2022-08-04 criteria provided, single submitter clinical testing Identified in unrelated patients with DCM, ARVC and unspecified skeletal myopathy in published literature (Campuzano et al. 2015; Forleo et al., 2017l Savarese et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as c.87711C>A p.(F29237) and c.68220 C>A p.(F22740L) due to use of alternate nomenclature/transcripts; This variant is associated with the following publications: (PMID: 34426522, 32039858, 24636144, 28750076, 26516846)
Blueprint Genetics RCV000208035 SCV000264286 uncertain significance Primary familial hypertrophic cardiomyopathy 2015-10-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV000619452 SCV000735687 uncertain significance Cardiovascular phenotype 2020-03-25 criteria provided, single submitter clinical testing The p.F22740L variant (also known as c.68220C>A), located in coding exon 170 of the TTN gene, results from a C to A substitution at nucleotide position 68220. The phenylalanine at codon 22740 is replaced by leucine, an amino acid with highly similar properties. This variant was detected in an individual with arrhythmogenic right ventricular cardiomyopathy who also had variants in the OBSCN gene (Forleo C et al. PLoS ONE, 2017 Jul;12:e0181842). 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.
Invitae RCV000643873 SCV000765560 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-12-19 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001170758 SCV001333364 uncertain significance Cardiomyopathy 2019-03-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000125950 SCV001748737 uncertain significance not specified 2022-07-19 criteria provided, single submitter clinical testing Variant summary: TTN c.87711C>A (p.Phe29237Leu) results in a non-conservative amino acid change located in the A-band domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-05 in 248118 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in TTN causing Dilated Cardiomyopathy (4e-05 vs 0.00039), allowing no conclusion about variant significance. c.87711C>A has been reported in the literature in individuals affected with Dilated Cardiomyopathy and ARVC (Campuzano_2015, Forleo_2017). 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. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV002498612 SCV002781971 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 2022-04-07 criteria provided, single submitter clinical testing
Revvity Omics, Revvity Omics RCV001813757 SCV003824829 uncertain significance not provided 2023-01-09 criteria provided, single submitter clinical testing

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