ClinVar Miner

Submissions for variant NM_001278716.2(FBXL4):c.618_621dup (p.Glu208fs) (rs886041625)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000298072 SCV000330325 pathogenic not provided 2018-12-07 criteria provided, single submitter clinical testing The c.618_621dupACTG pathogenic variant in the FBXL4 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.618_621dupACTG variant causes a frameshift starting with codon Glutamic acid 208, changes this amino acid to a Threonine residue, and creates a premature Stop codon at position 5 of the new reading frame, denoted p.Glu208ThrfsX5. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.618_621dupACTG variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.618_621dupACTG as a pathogenic variant.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000502064 SCV000598192 pathogenic Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) 2017-08-10 criteria provided, single submitter clinical testing The NM_012160.4:c.618_621dup (NP_036292.2:p.Glu208ThrfsTer5) [GRCH38: NC_000006.12:g.98917612_98917615dup] variant in FBXL4 gene is interpretated to be a Pathogenic based on ACMG guidelines (PMID: 25741868). This variant meets one or more of the following evidence codes reported in the ACMG-guideline. PVS1:This variant is a predcted null variant in FBXL4 where loss of function is a known mechanism of disease. PM2:This variant is absent in key population databases. PP4:Patient’s phenotype or family history is highly specific for FBXL4. PP5:Reputable source(s) suggest that the variant is pathogenic. Based on this evidence code ClinGen Pathogenicity Calculator (PMID:28081714) suggested that the variant is Pathogenic.

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