Submissions for variant NM_000941.3(POR):c.1660C>T (p.Arg554Ter) (rs782336856)

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Total submissions: 2

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Clinical Services Laboratory,Illumina	RCV000779538	SCV000916205	uncertain significance	Disordered steroidogenesis due to cytochrome p450 oxidoreductase deficiency	2017-08-28	criteria provided, single submitter	clinical testing	The POR c.1660C>T (p.Arg554Ter) variant is a stop-gained variant, which was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018) and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for cytochrome P450 oxidoreductase deficiency.
Invitae	RCV000779538	SCV001415888	pathogenic	Disordered steroidogenesis due to cytochrome p450 oxidoreductase deficiency	2019-06-24	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg554*) in the POR gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs782336856, ExAC 0.02%). This variant has not been reported in the literature in individuals with POR-related conditions. ClinVar contains an entry for this variant (Variation ID: 632506). Loss-of-function variants in POR are known to be pathogenic (PMID: 14758361, 20732302, 21741353). For these reasons, this variant has been classified as Pathogenic.

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