ClinVar Miner

Submissions for variant NM_001363711.2(DUOX2):c.4000C>T (p.Arg1334Trp)

gnomAD frequency: 0.00008  dbSNP: rs200541410
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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 RCV003058461 SCV003442835 uncertain significance not provided 2024-07-10 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 1334 of the DUOX2 protein (p.Arg1334Trp). This variant is present in population databases (rs200541410, gnomAD 0.07%). This missense change has been observed in individual(s) with congenital hypothyroidism (PMID: 25248169, 26349762, 26565538, 27108200, 27557340, 29650690). ClinVar contains an entry for this variant (Variation ID: 2137662). 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 DUOX2 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects DUOX2 function (PMID: 25248169, 26565538). 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.
Juno Genomics, Hangzhou Juno Genomics, Inc RCV004796761 SCV005418312 likely pathogenic Thyroid dyshormonogenesis 6 criteria provided, single submitter clinical testing PM2_Supporting+PP3_Moderate+PM3+PP4
Fulgent Genetics, Fulgent Genetics RCV004796761 SCV005637780 likely pathogenic Thyroid dyshormonogenesis 6 2024-06-19 criteria provided, single submitter clinical testing

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