ClinVar Miner

Submissions for variant NM_001395413.1(POR):c.804C>A (p.Ser268Arg)

dbSNP: rs201598971
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001986760 SCV002281951 uncertain significance Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency 2021-09-17 criteria provided, single submitter clinical testing This sequence change replaces serine with arginine at codon 271 of the POR protein (p.Ser271Arg). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and arginine. This variant is present in population databases (rs201598971, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with POR-related conditions. 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 RCV002282675 SCV002570663 uncertain significance not specified 2022-07-13 criteria provided, single submitter clinical testing Variant summary: POR c.813C>A (p.Ser271Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.9e-05 in 243866 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in POR causing Congenital Adrenal Hyperplasia (4.9e-05 vs 0.00091), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.813C>A in individuals affected with Congenital Adrenal Hyperplasia and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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