ClinVar Miner

Submissions for variant NM_138413.4(HOGA1):c.569C>T (p.Pro190Leu) (rs202047589)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000791690 SCV000930950 pathogenic not provided 2020-10-09 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 190 of the HOGA1 protein (p.Pro190Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs202047589, ExAC 0.06%). This variant has been observed in individual(s) with primary hyperoxaluria (PMID: 21896830, 22781098, 27561601). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 204273). Experimental studies have shown that this variant affects HOGA1 protein function (PMID: 22771891). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000186480 SCV002014910 pathogenic Primary hyperoxaluria, type III 2021-10-14 criteria provided, single submitter clinical testing Variant summary: HOGA1 c.569C>T (p.Pro190Leu) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.4e-05 in 251866 control chromosomes (gnomAD and publication data). This frequency is not significantly higher than expected for a pathogenic variant in HOGA1 causing Primary Hyperoxaluria, Type III (4.4e-05 vs 0.0015), allowing no conclusion about variant significance. c.569C>T has been reported in the literature in multiple individuals affected with Primary Hyperoxaluria, Type III (Monico_2011, Beck_2012, Martin-Higueras_2021). Additionally, this variant was found in three homozygous patients in one family and co-segregated with disease (Beck_2012). These data indicate that the variant is very likely to be associated with disease. Functional studies report experimental evidence evaluating an impact on protein function and this variant effect results in reducing expressed hHOGA protein level and hHOGA activity compared to wild-type in transfected cells (Riedel_2012, Beck_2012). Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic and likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Clinical Biochemistry Laboratory,Health Services Laboratory RCV000186480 SCV000239840 pathogenic Primary hyperoxaluria, type III 2014-11-27 no assertion criteria provided research
Natera, Inc. RCV000186480 SCV001453552 likely pathogenic Primary hyperoxaluria, type III 2020-09-16 no assertion criteria provided clinical testing
PerkinElmer Genomics RCV000791690 SCV002016616 likely pathogenic not provided 2021-09-08 no assertion criteria provided clinical testing

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