ClinVar Miner

Submissions for variant NM_017946.4(FKBP14):c.362dup (p.Glu122fs) (rs542489955)

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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000262568 SCV000329349 pathogenic not provided 2018-07-30 criteria provided, single submitter clinical testing The c.362dupC pathogenic variant in the FKBP14 gene has been reported previously in both the homozygous and compound heterozygous state in association with an autosomal recessive form of Ehlers-Danlos syndrome (Baumann et al., 2012; Murray et al., 2014; Dordoni et al., 2016; Giunta et al., 2017). Clinical features of individuals homozygous for the c.362dupC variant include congenital hypotonia, kyphoscoliosis, hypermobile joints, myopathy, and hearing loss (Baumann et al., 2012; Murray et al., 2014; Dordoni et al., 2016; Giunta et al., 2017). Vascular complications have also been reported (Murray et al., 2014; Dordoni et al., 2016). The c.362dupC variant causes a frameshift starting with codon Glutamic acid 122, changes this amino acid to an Arginine residue, and creates a premature Stop codon at position 7 of the new reading frame, denoted p.Glu122ArgfsX7. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is observed in 124/113688 (0.1%) alleles from individuals of European (Non-Finnish) background, in the gnomAD dataset, and no individuals were reported to be homozygous. We interpret c.362dupC as a pathogenic variant.
Invitae RCV000533832 SCV000652309 pathogenic Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss 2020-10-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu122Argfs*7) in the FKBP14 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs542489955, ExAC 0.1%). This variant has been reported to segregate with Ehlers-Danlos syndrome in a single family (PMID: 22265013). It has also been reported in several unrelated affected individuals in the homozygous state (PMID: 24677762, 22265013) and in combination with another FKBP14 variant in the other allele (PMID: 27149304, 22265013). ClinVar contains an entry for this variant (Variation ID: 279809). For these reasons, this variant has been classified as Pathogenic.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000262568 SCV000705359 likely pathogenic not provided 2017-01-09 criteria provided, single submitter clinical testing
Ambry Genetics RCV000623711 SCV000741479 pathogenic Inborn genetic diseases 2016-06-02 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000533832 SCV001369762 likely pathogenic Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss 2020-01-20 criteria provided, single submitter clinical testing This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2. This variant was detected in homozygous state.
Institute of Human Genetics, University of Leipzig Medical Center RCV000533832 SCV001429022 pathogenic Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss 2019-07-10 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000262568 SCV001448093 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Baylor Genetics RCV000533832 SCV001524457 pathogenic Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss 2019-03-26 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported in multiple affected families as disease-causing [PMID 22265013, 27905128, 28617417, 24677762]
Mayo Clinic Laboratories, Mayo Clinic RCV000262568 SCV001715926 pathogenic not provided 2020-07-23 criteria provided, single submitter clinical testing PVS1, PM3_Stromg, PP1
CeGaT Praxis fuer Humangenetik Tuebingen RCV000262568 SCV001747506 pathogenic not provided 2021-06-01 criteria provided, single submitter clinical testing
OMIM RCV000533832 SCV000045487 pathogenic Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss 2012-02-10 no assertion criteria provided literature only
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000415176 SCV000492576 pathogenic Congenital muscular dystrophy; Joint hypermobility; Thoracolumbar scoliosis; Pes valgus; Muscular hypotonia 2016-02-10 no assertion criteria provided clinical testing
Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes RCV000262568 SCV000778202 pathogenic not provided 2016-06-01 no assertion criteria provided clinical testing
GeneReviews RCV000533832 SCV000929975 pathogenic Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss 2019-05-23 no assertion criteria provided literature only
Research Centre for Medical Genetics,Federal State Budgetary Scientific Institution RCV000533832 SCV001593267 pathogenic Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss 2020-10-23 no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000262568 SCV001808321 pathogenic not provided no assertion criteria provided clinical testing

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