Submissions for variant NM_001395413.1(POR):c.560A>G (p.Tyr187Cys)

gnomAD frequency: 0.00003  dbSNP: rs782681272

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001164101	SCV001326202	uncertain significance	Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory 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, this variant 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 (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001164101	SCV002292280	uncertain significance	Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	2021-08-28	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine with cysteine at codon 190 of the POR protein (p.Tyr190Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs782681272, ExAC 0.2%). This variant has not been reported in the literature in individuals affected with POR-related conditions. ClinVar contains an entry for this variant (Variation ID: 911569). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004690000	SCV005185247	uncertain significance	not specified	2024-05-20	criteria provided, single submitter	clinical testing
3billion, Medical Genetics	RCV004726909	SCV005328872	likely benign	Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis; Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency	2024-09-20	criteria provided, single submitter	clinical testing	The homozygous variant was found in patients diagnosed with another variant in a different gene, with no symptoms related to the gene containing the homozygous variant.