Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001855620 | SCV002230094 | pathogenic | Bifunctional peroxisomal enzyme deficiency; Perrault syndrome | 2023-04-08 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on HSD17B4 protein function. ClinVar contains an entry for this variant (Variation ID: 559068). This missense change has been observed in individual(s) with D-bifunctional protein deficiency (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs771780974, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 251 of the HSD17B4 protein (p.Arg251Trp). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003235343 | SCV003934504 | uncertain significance | not specified | 2023-05-16 | criteria provided, single submitter | clinical testing | Variant summary: HSD17B4 c.751C>T (p.Arg251Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 250770 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.751C>T in individuals affected with D-Bifunctional Protein Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Mayo Clinic Laboratories, |
RCV000676077 | SCV000801812 | uncertain significance | not provided | 2018-02-15 | no assertion criteria provided | clinical testing |