Submissions for variant NM_001032386.2(SUOX):c.796G>A (p.Gly266Ser)

gnomAD frequency: 0.00002  dbSNP: rs144064367

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Mendelics	RCV000988862	SCV001138755	likely pathogenic	Sulfite oxidase deficiency	2019-05-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001175544	SCV001339165	uncertain significance	not specified	2020-03-02	criteria provided, single submitter	clinical testing	Variant summary: SUOX c.796G>A (p.Gly266Ser) results in a non-conservative amino acid change located in the Oxidoreductase, molybdopterin-binding domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.4e-05 in 251446 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in SUOX causing Sulfite oxidase deficiency (4.4e-05 vs 0.0011), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.796G>A in individuals affected with sulfite oxidase deficiency 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 likely pathogenic. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae	RCV000988862	SCV002162072	uncertain significance	Sulfite oxidase deficiency	2022-06-13	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 266 of the SUOX protein (p.Gly266Ser). This variant is present in population databases (rs144064367, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SUOX-related conditions. ClinVar contains an entry for this variant (Variation ID: 802863). 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.
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine	RCV000988862	SCV002820173	uncertain significance	Sulfite oxidase deficiency		criteria provided, single submitter	clinical testing	The missense variant p.G266S in SUOX (NM_000456.2) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. It has been submitted in the ClinVar database as Likely Pathogenic but no supporting evidence for the same is available.There is a small physicochemical difference between glycine and serine, which is not likely to impact secondary protein structure as these residues share similar properties. The p.G266S missense variant is predicted to be damaging by both SIFT and PolyPhen2. The glycine residue at codon 266 of SUOX is conserved in all mammalian species. The nucleotide c.796 in SUOX is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.
Revvity Omics, Revvity	RCV000988862	SCV003818148	uncertain significance	Sulfite oxidase deficiency	2020-03-18	criteria provided, single submitter	clinical testing