Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000255053 | SCV000321538 | pathogenic | not provided | 2023-03-24 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect resulting in almost complete loss of enzyme activity (Laflamme et al., 1996; Sahakitrungruang et al., 2009); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 14671162, 12573489, 19470621, 21340163, 8550762, 31589614, 25697092, 30229581, 29255217, 27271787, 33547012, 29144824, 24485502, 31034465, Mohnach[CaseReport]2018) |
Genetic Services Laboratory, |
RCV000501502 | SCV000594286 | pathogenic | Deficiency of steroid 17-alpha-monooxygenase | 2016-09-26 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000501502 | SCV000893835 | pathogenic | Deficiency of steroid 17-alpha-monooxygenase | 2021-08-17 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000255053 | SCV001415980 | pathogenic | not provided | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 96 of the CYP17A1 protein (p.Arg96Trp). This variant is present in population databases (rs104894138, gnomAD 0.006%). This missense change has been observed in individuals with congenital adrenal hyperplasia (PMID: 8550762, 21340163, 28008861). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1785). 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%. Experimental studies have shown that this missense change affects CYP17A1 function (PMID: 8550762, 10720067). This variant disrupts the p.Arg96 amino acid residue in CYP17A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16569739, 21846181, 23291414, 23466679, 26543560, 28008861). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003114170 | SCV003800630 | pathogenic | Congenital adrenal hyperplasia | 2023-01-30 | criteria provided, single submitter | clinical testing | Variant summary: CYP17A1 c.286C>T (p.Arg96Trp) 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 2.8e-05 in 251326 control chromosomes (gnomAD). c.286C>T has been reported in the literature in multiple individuals affected with Congenital Adrenal Hyperplasia/17 alpha-hydroxylase/17,20-lyase deficiency (e.g. Laflamme_1996, Biason-Lauber_2000, Costenaro_2010). These data indicate that the variant is very likely to be associated with disease. Experimental studies examining the effect of the variant on protein function have shown that it results in an enzyme activity of approximately 10%-30% of the normal WT protein (e.g. Laflamme_1996, Biason-Lauber_2000). Five submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Baylor Genetics | RCV000501502 | SCV004215398 | pathogenic | Deficiency of steroid 17-alpha-monooxygenase | 2023-08-23 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000001858 | SCV000022014 | pathogenic | 17-alpha-hydroxylase/17,20-lyase deficiency, combined complete | 2003-12-01 | no assertion criteria provided | literature only | |
Natera, |
RCV000501502 | SCV002091218 | pathogenic | Deficiency of steroid 17-alpha-monooxygenase | 2020-09-22 | no assertion criteria provided | clinical testing |