Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000666888 | SCV000791257 | likely pathogenic | Bifunctional peroxisomal enzyme deficiency | 2017-05-15 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000805184 | SCV000945131 | pathogenic | Bifunctional peroxisomal enzyme deficiency; Perrault syndrome | 2019-02-01 | criteria provided, single submitter | clinical testing | Loss-of-function variants in HSD17B4 are known to be pathogenic (PMID: 11810648, 16385454). For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individuals affected with D-bifunctional protein deficiency (PMID: 16385454). This variant is present in population databases (rs751646311, ExAC 0.002%). This sequence change creates a premature translational stop signal (p.Gln677*) in the HSD17B4 gene. It is expected to result in an absent or disrupted protein product. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000666888 | SCV001362502 | pathogenic | Bifunctional peroxisomal enzyme deficiency | 2019-05-20 | criteria provided, single submitter | clinical testing | Variant summary: HSD17B4 c.2029C>T (p.Gln677X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4e-06 in 251098 control chromosomes (gnomAD). c.2029C>T has been reported in the literature in a homozygous individual affected with D-Bifunctional Protein Deficiency type I (Ferdinandusse_2006). This study also reported experimental evidence evaluating an impact on protein function, and demonstrated the complete lack of protein and enzymatic activity in patient derived fibroblasts (Ferdinandusse_2006). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Revvity Omics, |
RCV001784241 | SCV002025034 | pathogenic | not provided | 2021-04-01 | criteria provided, single submitter | clinical testing | |
| Clinical Laboratory Sciences Program |
RCV000666888 | SCV003927916 | pathogenic | Bifunctional peroxisomal enzyme deficiency | 2023-04-01 | no assertion criteria provided | clinical testing |