ClinVar Miner

Submissions for variant NM_138413.4(HOGA1):c.860G>T (p.Gly287Val) (rs138207257)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000000047 SCV000789310 likely pathogenic Primary hyperoxaluria, type III 2017-01-27 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000000047 SCV000915488 pathogenic Primary hyperoxaluria, type III 2018-12-16 criteria provided, single submitter clinical testing The HOGA1 c.860G>T (p.Gly287Val) missense variant was first reported by Belostotsky et al. (2010) in a non-consanguineous Ashkenazi Jewish family with primary hyperoxaluria type 3. Five affected children were found to be compound heterozygous for the p.Gly287Val variant and a second variant. Additionally, the variant has been reported in at least three further cases in a compound heterozygous state (Monico et al., 2011 and Williams et al., 2012). Riedel et al. (2012) found that protein products of the p.Gly287Val variant were unstable, had a tendency to aggregate, and retained no measurable activity, as compared to the wild type protein. Control data are unavailable for this variant, which is reported at a frequency of 0.001588 in the Asjkenazi Jewish population of the Genome Aggregation Database. Based on the collective evidence the HOGA1 p.Gly287Val variant is classified as pathogenic for primary hyperoxaluria. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000798240 SCV000937843 pathogenic not provided 2018-07-23 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 287 of the HOGA1 protein (p.Gly287Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs138207257, ExAC 0.02%). This variant has been observed to be homozygous or in combination with another HOGA1 variant in individuals affected with primary hyperoxaluria (PMID: 21896830, 22391140, 27561601), and has been shown to segregate with disease in a family (PMID: 20797690). ClinVar contains an entry for this variant (Variation ID: 30). Experimental studies have shown that this missense change leads to HOGA1 protein instability (PMID: 22771891). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000000047 SCV000020190 pathogenic Primary hyperoxaluria, type III 2010-09-10 no assertion criteria provided literature only
Clinical Biochemistry Laboratory,Health Services Laboratory RCV000000047 SCV000239846 pathogenic Primary hyperoxaluria, type III 2014-11-27 no assertion criteria provided in vitro Prediction programme. Found in conjunction with c.700+5G>T.

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