ClinVar Miner

Submissions for variant NM_181457.4(PAX3):c.812G>A (p.Arg271His) (rs774528745)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000372931 SCV000329634 pathogenic not provided 2016-09-07 criteria provided, single submitter clinical testing he R271H pathogenic variant in the PAX3 gene has been reported previously as a de novo change in an individual with Waardenburg syndrome type 1 (Tassabehji et. al, 1995). Other missense variant in the same residue (R271G, R271C) have also been reported in the Human Gene Mutation Database in association with Waardenburg syndrome (Stenson et al., 2014), supporting the functional importance of this residue. Functional studies have demonstrated that the R271G variant in this residue abolishes the DNA binding of both PAX3 protein domains (Fortin et al., 1997). The R271H variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. 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. We interpret R271H as a pathogenic variant.
Center for Human Genetics, Inc RCV000660219 SCV000782219 pathogenic Waardenburg syndrome type 1 2016-11-01 criteria provided, single submitter clinical testing

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