ClinVar Miner

Submissions for variant NM_022455.4(NSD1):c.5951G>C (p.Arg1984Pro) (rs587784169)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489406 SCV000577155 pathogenic not provided 2017-04-10 criteria provided, single submitter clinical testing The apparently de novo R1984P variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R1984P variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R1984P variant 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 in the SET domain at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, different missense variants at the same codon (R1984G and R1984Q) have been reported in Human Gene Mutation Database in association with Sotos syndrome (de et al., 2004; Rio et al., 2003; Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, we interpret R1984P as a pathogenic variant.

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