ClinVar Miner

Submissions for variant NM_000102.4(CYP17A1):c.286C>T (p.Arg96Trp) (rs104894138)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255053 SCV000321538 pathogenic not provided 2015-12-18 criteria provided, single submitter clinical testing The R96W missense variant in the CYP17A1 gene has been reported previously in association with 17 alpha-hydroxylase/17,20-lyase deficiency (Costenaro et al., 2010; Martin et al., 2003). R96W was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Functional studies have shown that R96W significantly impairs or abolishes 17 alpha-hydroxylase activity (LaFlamme et al., 1996; Sahakitrungruang et al, 2009).
Genetic Services Laboratory,University of Chicago RCV000501502 SCV000594286 pathogenic Deficiency of steroid 17-alpha-monooxygenase 2016-09-26 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000501502 SCV000893835 pathogenic Deficiency of steroid 17-alpha-monooxygenase 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000255053 SCV001415980 pathogenic not provided 2019-10-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 96 of the CYP17A1 protein (p.Arg96Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs104894138, ExAC 0.006%). This variant has been observed in individuals and families with congenital adrenal hyperplasia (PMID: 8550762, 28008861, 21340163). ClinVar contains an entry for this variant (Variation ID: 1785). This variant has been reported to affect CYP17A1 protein 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, 28008861, 26543560, 23466679, 23291414, 21846181). 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.
OMIM RCV000001858 SCV000022014 pathogenic Complete combined 17-alpha-hydroxylase/17,20-lyase deficiency 2003-12-01 no assertion criteria provided literature only

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