ClinVar Miner

Submissions for variant NM_001167.4(XIAP):c.562G>A (p.Gly188Arg)

dbSNP: rs1602544454
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000822305 SCV000963103 uncertain significance X-linked lymphoproliferative disease due to XIAP deficiency 2023-10-03 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 188 of the XIAP protein (p.Gly188Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with suspected XIAP deficiency and/or very early onset inflammatory bowel disease (PMID: 24616127, 30755392). ClinVar contains an entry for this variant (Variation ID: 664245). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt XIAP protein function. Experimental studies have shown that this missense change affects XIAP function (PMID: 27317434). 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.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV000822305 SCV003806830 likely pathogenic X-linked lymphoproliferative disease due to XIAP deficiency 2022-03-16 criteria provided, single submitter clinical testing ACMG classification criteria: PS3 supporting, PS4 supporting, PM2 moderated, PM5 moderated, PP3 supporting
Center for Personalized Medicine, Children's Hospital Los Angeles RCV003156136 SCV003845326 likely pathogenic See cases 2022-12-21 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV003480873 SCV004227699 likely pathogenic not provided 2023-02-08 criteria provided, single submitter clinical testing PP3, PM1, PM2_supporting, PM5, PS4_moderate
GeneDx RCV003480873 SCV005324999 likely pathogenic not provided 2023-06-28 criteria provided, single submitter clinical testing Identified in patients with suspected XIAP deficiency in published literature (Gifford et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 24616127, 30755392, 23818254, 19398375)

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