ClinVar Miner

Submissions for variant NM_006147.4(IRF6):c.16C>T (p.Arg6Cys) (rs28942094)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413551 SCV000490567 likely pathogenic not provided 2016-07-13 criteria provided, single submitter clinical testing The R6C variant has been published previously in association with van der Woude syndrome (Wang et al., 2003; de Lima et al., 2009; Desmyter et al., 2010). The variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. R6C is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in the same residue (R6L/P) and in nearby residues (A2V, R9W/Q, P12L) have been reported in the Human Gene Mutation Database in association with van der Woude syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is likely pathogenic.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000414901 SCV000492827 pathogenic Cleft palate 2015-08-31 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000762880 SCV000893260 pathogenic Orofacial cleft 6, susceptibility to; Popliteal pterygium syndrome; van der Woude syndrome 1 2018-10-31 criteria provided, single submitter clinical testing
OMIM RCV000003586 SCV000023744 pathogenic van der Woude syndrome 1 2003-10-01 no assertion criteria provided literature only

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