Submissions for variant NM_138413.4(HOGA1):c.107C>T (p.Ala36Val) (rs201803986)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Clinical Services Laboratory,Illumina	RCV000186472	SCV000366314	likely pathogenic	Primary hyperoxaluria, type III	2017-04-27	criteria provided, single submitter	clinical testing	The HOGA1 c.107C>T (p.Ala36Val) missense variant has been reported in three studies in which it is found in at least three patients with primary hyperoxaluria type III (PH3) in a compound heterozygous state and in a heterozygous state in one additional patient who also carried a heterozygous deletion in the AGXT gene, which is associated with PH1 (Williams et al. 2012; Pitt et al. 2014; Williams et al. 2015). Control data are unavailable for this variant, which is reported at a frequency of 0.00024 in the European (non-Finnish) population of the Exome Aggregation Consortium. Analysis of levels of the metabolic precursor of the HOGA1 substrate revealed that PH3 patients had significantly higher levels compared to age-matched controls, and that parental carriers showed moderate but significant increases in levels (Pitt et al. 2014). Based on the evidence, the p.Ala36Val variant is classified as likely pathogenic for primary hyperoxaluria. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Clinical Biochemistry Laboratory,Health Services Laboratory	RCV000186472	SCV000239830	pathogenic	Primary hyperoxaluria, type III	2014-11-27	no assertion criteria provided	in vitro	Predicted benign but found in trans with c.700+5G>T and c.944_946del. Also found by Pitt et al., 2014 (PMID:24563386).