ClinVar Miner

Submissions for variant NM_001363711.2(DUOX2):c.2635G>A (p.Glu879Lys)

gnomAD frequency: 0.00001  dbSNP: rs774556391
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Revvity Omics, Revvity RCV001781011 SCV002017346 likely pathogenic Thyroid dyshormonogenesis 6 2021-05-12 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002034589 SCV002116543 pathogenic not provided 2024-03-19 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 879 of the DUOX2 protein (p.Glu879Lys). This variant is present in population databases (rs774556391, gnomAD 0.1%). This missense change has been observed in individual(s) with congenital hypothyroidism (PMID: 18765513, 25248169, 26349762, 26709262, 29650690, 32425884). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1324306). 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). For these reasons, this variant has been classified as Pathogenic.
Juno Genomics, Hangzhou Juno Genomics, Inc RCV001781011 SCV005417875 pathogenic Thyroid dyshormonogenesis 6 criteria provided, single submitter clinical testing PM3_VeryStrong+PP4+PS3_Supporting
Fulgent Genetics, Fulgent Genetics RCV001781011 SCV005630721 likely pathogenic Thyroid dyshormonogenesis 6 2024-05-23 criteria provided, single submitter clinical testing

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