Submissions for variant NM_001363711.2(DUOX2):c.4080G>T (p.Lys1360Asn)

dbSNP: rs374891282

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001875773	SCV002271983	uncertain significance	not provided	2024-03-01	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 1360 of the DUOX2 protein (p.Lys1360Asn). This variant also falls at the last nucleotide of exon 30, which is part of the consensus splice site for this exon. This variant is present in population databases (rs374891282, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with DUOX2-related conditions. ClinVar contains an entry for this variant (Variation ID: 917856). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Department of Pediatrics, Division of Medical Genetics, Faculty of Medicine Ramathibodi Hospital, Mahidol University	RCV001175130	SCV001250737	likely pathogenic	Thyroid dyshormonogenesis 6	2020-05-14	no assertion criteria provided	research	The patient showed classical presentation of transient congenital primary hypothyroidism with enlarged thyroid on thyroid scintigraphy.