ClinVar Miner

Submissions for variant NM_138413.4(HOGA1):c.133C>G (p.Pro45Ala)

gnomAD frequency: 0.00001  dbSNP: rs1380918472
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003770420 SCV004614285 likely pathogenic not provided 2023-11-13 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 45 of the HOGA1 protein (p.Pro45Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with HOGA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 989900). 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 HOGA1 protein function with a positive predictive value of 95%. This variant disrupts the p.Pro45 amino acid residue in HOGA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26342005; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
Natera, Inc. RCV001277805 SCV001464777 uncertain significance Primary hyperoxaluria type 3 2020-04-11 no assertion criteria provided clinical testing

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