Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001067683 | SCV001232754 | pathogenic | not provided | 2024-01-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 96 of the CYP17A1 protein (p.Arg96Gln). This variant is present in population databases (rs104894153, gnomAD 0.004%). This missense change has been observed in individuals with autosomal recessive congenital adrenal hyperplasia (PMID: 16569739, 21846181, 23291414, 23466679, 26543560, 28008861). ClinVar contains an entry for this variant (Variation ID: 1802). 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) performed at Invitae indicates that this missense variant is expected to disrupt CYP17A1 protein function with a positive predictive value of 95%. This variant disrupts the p.Arg96 amino acid residue in CYP17A1. Other variant(s) that disrupt this residue have been observed in individuals with CYP17A1-related conditions (PMID: 8550762, 21340163), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002298430 | SCV002598545 | pathogenic | Congenital adrenal hyperplasia | 2022-09-01 | criteria provided, single submitter | clinical testing | Variant summary: CYP17A1 c.287G>A (p.Arg96Gln) results in a conservative amino acid change in the encoded protein sequence. Four 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 251342 control chromosomes. c.287G>A has been reported in the literature as homozygous or compound heterozygous genotypes in multiple individuals affected with features of combined 17-alpha hydroxylase/17,20-Lyase deficiency, a rare cause of autosomal recessive Congenital Adrenal Hyperplasia (example, Brooke_2006, Tian_2012, Athanasoulia_2013, Mula-Abed_2014, Deeb_2015, Camtosun_2017). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function demonstrating a complete inability to convert pregnenolone to 17-alpha hydroxypregenolone and DHEA, although the results as reported are not quantified as residual activity (example, Brooks_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. |
| Clinical Biochemistry Laboratory, |
RCV003460404 | SCV004190340 | pathogenic | Deficiency of steroid 17-alpha-monooxygenase | 2023-11-20 | criteria provided, single submitter | clinical testing | ACMG:PS5 PM1 PM2 PP3 PP4 PP5 |
| Baylor Genetics | RCV003460404 | SCV004215415 | pathogenic | Deficiency of steroid 17-alpha-monooxygenase | 2023-05-27 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000001875 | SCV000022031 | pathogenic | 17-alpha-hydroxylase/17,20-lyase deficiency, combined complete | 2006-06-01 | no assertion criteria provided | literature only |