Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV000005148 | SCV002769434 | pathogenic | Testosterone 17-beta-dehydrogenase deficiency | 2021-05-06 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with HSD17B3-related 17 beta-hydroxysteroid dehydrogenase deficiency (MIM#264300). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from serine to leucine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (5 heterozygotes, 0 homozygotes). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated short chain dehydrogenase (Decipher). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. The variant has been previously reported in multiple patients with HSD17B3-related 17 beta-hydroxysteroid dehydrogenase deficiency (MIM#264300) (PMID: 8075637, 17466011, 28739554, 30668521). (SP) 0901 - This variant has strong evidence for segregation with disease. The variant has been shown to segregate with disease in one family (PMID: 17466011). (SP) 1002 - This variant has moderate functional evidence supporting abnormal protein function. Site-directed mutagenesis study shows that this variant causes enzyme inactivation (PMID: 8075637). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Labcorp Genetics |
RCV002512796 | SCV003283810 | pathogenic | not provided | 2024-12-09 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 232 of the HSD17B3 protein (p.Ser232Leu). This variant is present in population databases (rs28939085, gnomAD 0.006%). This missense change has been observed in individuals with 17-beta-hydroxysteroid dehydrogenase type 3 deficiency (PMID: 8075637, 17466011, 28739554). ClinVar contains an entry for this variant (Variation ID: 4872). Invitae Evidence 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 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 HSD17B3 protein function. Experimental studies have shown that this missense change affects HSD17B3 function (PMID: 8075637). For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000005148 | SCV000025325 | pathogenic | Testosterone 17-beta-dehydrogenase deficiency | 1994-05-01 | no assertion criteria provided | literature only |