Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000811384 | SCV000951649 | pathogenic | Bifunctional peroxisomal enzyme deficiency; Perrault syndrome | 2023-12-14 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr568*) in the HSD17B4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HSD17B4 are known to be pathogenic (PMID: 11810648, 16385454, 20673864). This variant is present in population databases (no rsID available, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with Perrault syndrome (PMID: 20673864). ClinVar contains an entry for this variant (Variation ID: 655256). For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001260323 | SCV001437248 | pathogenic | Bifunctional peroxisomal enzyme deficiency | 2020-09-17 | criteria provided, single submitter | clinical testing | Variant summary: HSD17B4 c.1704T>A (p.Tyr568X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 250998 control chromosomes (gnomAD). c.1704T>A has been reported in the literature in individuals affected with Perrault syndrome (Pierce_2010). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Gene |
RCV001556667 | SCV001778289 | pathogenic | not provided | 2021-01-11 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 20673864, 27650058, 22037954, 26243799, 27790638, 28017249, 28830375, 31455392) |
Revvity Omics, |
RCV001556667 | SCV003825245 | pathogenic | not provided | 2021-12-08 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV001260323 | SCV004192378 | pathogenic | Bifunctional peroxisomal enzyme deficiency | 2023-10-02 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000023153 | SCV000044444 | pathogenic | Perrault syndrome 1 | 2010-08-13 | no assertion criteria provided | literature only | |
Natera, |
RCV001260323 | SCV002075425 | pathogenic | Bifunctional peroxisomal enzyme deficiency | 2021-08-11 | no assertion criteria provided | clinical testing | |
Gene |
RCV002538095 | SCV003525951 | not provided | Perrault syndrome | no assertion provided | literature only |