ClinVar Miner

Submissions for variant NM_000102.4(CYP17A1):c.1117C>G (p.His373Asp)

dbSNP: rs1423560123
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001376808 SCV001573979 likely pathogenic not provided 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 373 of the CYP17A1 protein (p.His373Asp). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.His373 amino acid residue in CYP17A1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8245018, 10877510, 11549876, 12706306, 24140098, 29278670). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Experimental studies have shown that this missense change affects CYP17A1 function (PMID: 19470621). 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. ClinVar contains an entry for this variant (Variation ID: 1065951). This missense change has been observed in individual(s) with 17alpha-hydroxylase deficiency (PMID: 19470621). This variant is not present in population databases (gnomAD no frequency).
MGZ Medical Genetics Center RCV001826121 SCV002579750 pathogenic Deficiency of steroid 17-alpha-monooxygenase 2021-12-22 criteria provided, single submitter clinical testing
Baylor Genetics RCV001826121 SCV004215408 likely pathogenic Deficiency of steroid 17-alpha-monooxygenase 2023-07-07 criteria provided, single submitter clinical testing
Natera, Inc. RCV001826121 SCV002094216 likely pathogenic Deficiency of steroid 17-alpha-monooxygenase 2021-03-04 no assertion criteria provided clinical testing

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