ClinVar Miner

Submissions for variant NM_000102.4(CYP17A1):c.1226C>G (p.Pro409Arg)

gnomAD frequency: 0.00002  dbSNP: rs367833709
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Revvity Omics, Revvity RCV001780601 SCV002018097 pathogenic Deficiency of steroid 17-alpha-monooxygenase 2019-05-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001885149 SCV002237753 pathogenic not provided 2024-07-24 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 409 of the CYP17A1 protein (p.Pro409Arg). This variant is present in population databases (rs367833709, gnomAD 0.03%). This missense change has been observed in individual(s) with 17-alpha-hydroxylase deficiency (PMID: 11243732, 20170344, 22087567, 22954317). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as g.5582C>G. ClinVar contains an entry for this variant (Variation ID: 1322182). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects CYP17A1 function (PMID: 11243732, 23291414). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV001780601 SCV002815581 pathogenic Deficiency of steroid 17-alpha-monooxygenase 2021-12-22 criteria provided, single submitter clinical testing
Baylor Genetics RCV001780601 SCV004215443 pathogenic Deficiency of steroid 17-alpha-monooxygenase 2024-03-06 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003401710 SCV004110119 pathogenic CYP17A1-related disorder 2024-03-15 no assertion criteria provided clinical testing The CYP17A1 c.1226C>G variant is predicted to result in the amino acid substitution p.Pro409Arg. This variant (also known as g.5582C>G) was reported in the compound heterozygous state in individuals with 17-alpha-hydroxylase deficiency (Lam et al 2001. PubMed ID: 11243732; Bee and Papari-Zareei. 2012. PubMed ID: 22087567). Functional studies also indicate this variant impacts 17-alpha-hydroxylase activity (Lam et al 2001. PubMed ID: 11243732; Han et al. 2013. PubMed ID: 23291414). This variant is reported in 0.030% of alleles in individuals of East Asian descent in gnomAD. This variant is interpreted as 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.