ClinVar Miner

Submissions for variant NM_006147.4(IRF6):c.1210G>A (p.Glu404Lys)

dbSNP: rs769068305
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000430826 SCV000517280 likely pathogenic not provided 2023-10-23 criteria provided, single submitter clinical testing Identified in individuals with Van der Woude spectrum in the published literature (PMID: 19282774, 29115498); Published functional studies demonstrate a damaging effect on periderm development (PMID: 28945736); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 19282774, 29115498, 28945736)
Labcorp Genetics (formerly Invitae), Labcorp RCV002229128 SCV000638964 pathogenic Orofacial cleft 6, susceptibility to; Popliteal pterygium syndrome; Van der Woude syndrome 2021-09-26 criteria provided, single submitter clinical testing Experimental studies have shown that this missense change affects IRF6 function (PMID: 28945736). This sequence change replaces glutamic acid with lysine at codon 404 of the IRF6 protein (p.Glu404Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with Van der Woude syndrome (PMID: 19282774, 29115498). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 217873). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005016559 SCV005645205 likely pathogenic Orofacial cleft 6, susceptibility to; Van der Woude syndrome 1; Autosomal dominant popliteal pterygium syndrome 2024-01-04 criteria provided, single submitter clinical testing
Mendelics RCV000201948 SCV000256869 pathogenic Van der Woude syndrome 1 2014-06-02 no assertion criteria provided clinical testing

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