ClinVar Miner

Submissions for variant NM_001363711.2(DUOX2):c.1295G>A (p.Arg432His)

gnomAD frequency: 0.00004  dbSNP: rs530736554
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001877149 SCV002135866 uncertain significance not provided 2024-11-25 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 432 of the DUOX2 protein (p.Arg432His). This variant is present in population databases (rs530736554, gnomAD 0.05%). This missense change has been observed in individual(s) with autosomal recessive thyroid dyshormonogenesis and/or congenital hypothyroidism (PMID: 30154845, 33631011, 34564849). ClinVar contains an entry for this variant (Variation ID: 1370407). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt DUOX2 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects DUOX2 function (PMID: 34564849). 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.
PreventionGenetics, part of Exact Sciences RCV003434340 SCV004116508 likely pathogenic DUOX2-related disorder 2023-05-24 criteria provided, single submitter clinical testing The DUOX2 c.1295G>A variant is predicted to result in the amino acid substitution p.Arg432His. This variant has been reported in the compound heterozygous state in individuals with thyroid dyshormonogenesis or congenital hypothyroidism (Patient ID 15, Chen et al. 2018. PubMed ID: 30154845; Patient ID 28, Wang et al. 2020. PubMed ID: 32319661). This variant was also identified in another study in individuals with congenital hypothyroidism, however additional details were not provided (Wang et al. 2021. PubMed ID: 33631011). This variant is reported in 0.055% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/15-45401090-C-T). This variant is interpreted as likely pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005006126 SCV005630748 likely pathogenic Thyroid dyshormonogenesis 6 2024-06-06 criteria provided, single submitter clinical testing

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