ClinVar Miner

Submissions for variant NM_014362.4(HIBCH):c.852del (p.Leu284fs) (rs1131692017)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493651 SCV000583375 pathogenic not provided 2017-12-21 criteria provided, single submitter clinical testing The c.852delA variant in the HIBCH gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.852delA variant causes a frameshift starting with codon Leucine 284, changes this amino acid to a Phenylalanine residue, and creates a premature Stop codon at position 10 of the new reading frame, denoted p.Leu284PhefsX10. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.852delA variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.852delA as a pathogenic variant.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV001195536 SCV001365914 likely pathogenic Beta-hydroxyisobutyryl-CoA deacylase deficiency 2019-08-09 criteria provided, single submitter clinical testing The p.Leu284PhefsX10 variant in HIBCH has not been reported in any other families with HIBCH deficiency and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 284 and leads to a premature termination codon 10 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function variants in the HIBCH gene have been reported in several individuals with HIBCH deficiency. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive HIBCH deficiency. ACMG/AMP Criteria applied: PVS1, PM2.

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