ClinVar Miner

Submissions for variant NM_022455.4(NSD1):c.5842C>T (p.Arg1948Cys) (rs886041941)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000366914 SCV000330750 pathogenic not provided 2017-10-12 criteria provided, single submitter clinical testing The R1948C variant in the NSD1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The R1948C variant is not observed in large population cohorts (Lek et al., 2016). Although this substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species, the R1948C variant is a non-conservative amino acid substitution within the SET protein domain, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in the same residue (R1948G) has been reported in association with Sotos syndrome (Pohjola et al., 2012), supporting the functional importance of this residue of the protein. We interpret R1948C as a pathogenic variant.

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