ClinVar Miner

Submissions for variant NM_017807.4(OSGEP):c.973C>T (p.Arg325Trp)

gnomAD frequency: 0.00003  dbSNP: rs761839638
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522704 SCV000618024 likely pathogenic not provided 2017-10-18 criteria provided, single submitter clinical testing The R325W variant in the OSGEP gene has been reported previously, in trans with the K78E variant in this patient (Braun et al., 2017). In addition, another variant at the same residue, R325Q, has been reported, either in the homozygous state or in trans with a second OSGEP variant, in multiple individuals with clinical features of Galloway-Mowat syndrome (Braun et al., 2017; Edvardson et al., 2017). The R325W variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In addition, the R325W substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R325W as a likely pathogenic variant.
Ambry Genetics RCV001266639 SCV001444815 likely pathogenic Inborn genetic diseases 2018-08-27 criteria provided, single submitter clinical testing
Baylor Genetics RCV001335865 SCV001529114 uncertain significance Galloway-Mowat syndrome 3 2018-06-20 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp RCV000522704 SCV003442775 uncertain significance not provided 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 325 of the OSGEP protein (p.Arg325Trp). This variant is present in population databases (rs761839638, gnomAD 0.07%). This missense change has been observed in individual(s) with Galloway-Mowat syndrome (PMID: 28805828). ClinVar contains an entry for this variant (Variation ID: 449687). 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. Experimental studies have shown that this missense change affects OSGEP function (PMID: 28805828). This variant disrupts the p.Arg325 amino acid residue in OSGEP. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 28272532, 30141175). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

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