ClinVar Miner

Submissions for variant NM_000102.4(CYP17A1):c.316T>C (p.Ser106Pro)

gnomAD frequency: 0.00001  dbSNP: rs104894135
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000288112 SCV000329841 pathogenic not provided 2019-08-12 criteria provided, single submitter clinical testing Published functional studies demonstrate a decreased 17 alpha hydroxylase activity in comparison to wildtype (Lin et al., 1991); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 7811386, 14560315, 1714904, 1621662, 25697092, 27096365, 29278670, 16477341)
Fulgent Genetics, Fulgent Genetics RCV000763211 SCV000893834 pathogenic Deficiency of steroid 17-alpha-monooxygenase 2018-10-31 criteria provided, single submitter clinical testing
Baylor Genetics RCV000763211 SCV004215421 pathogenic Deficiency of steroid 17-alpha-monooxygenase 2023-04-18 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000288112 SCV004295709 pathogenic not provided 2023-08-24 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects CYP17A1 function (PMID: 1714904). 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 not expected to disrupt CYP17A1 protein function. ClinVar contains an entry for this variant (Variation ID: 1780). This missense change has been observed in individual(s) with 17-alpha-hydroxylase deficiency (PMID: 1714904, 16477341). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs104894135, gnomAD 0.006%). This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 106 of the CYP17A1 protein (p.Ser106Pro).
OMIM RCV000001852 SCV000022008 pathogenic 17-alpha-hydroxylase/17,20-lyase deficiency, combined complete 1992-05-01 no assertion criteria provided literature only
Natera, Inc. RCV000763211 SCV002091107 pathogenic Deficiency of steroid 17-alpha-monooxygenase 2021-08-10 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV003914797 SCV004733170 likely pathogenic CYP17A1-related disorder 2023-12-18 no assertion criteria provided clinical testing The CYP17A1 c.316T>C variant is predicted to result in the amino acid substitution p.Ser106Pro. This variant has been reported in the homozygous and compound heterozygous states in multiple individuals with 17-alpha-hydroxylase/17,20 lyase deficiency (Lin et al. 1991. PubMed ID: 1714904; Wong et al. 2006. PubMed ID: 16477341; Zhang et al. 2015. PubMed ID: 25697092; Sun et al. 2017. PubMed ID: 29278670). In vitro experimental studies have demonstrated that the p.Ser106Pro variant results in a complete loss of catalytic activity when co-incubated with several different steroid substrates (Lin et al. 1991. PubMed ID: 1714904). This variant is reported in 0.011% of alleles in individuals of East Asian descent in gnomAD. This variant is interpreted as likely pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.