ClinVar Miner

Submissions for variant NM_022455.5(NSD1):c.4847A>G (p.His1616Arg)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001042135 SCV001205799 pathogenic Beckwith-Wiedemann syndrome 2019-11-22 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 1616 of the NSD1 protein (p.His1616Arg). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with an overgrowth syndrome (PMID: 28475857, Invitae). In at least one individual the variant was observed to be de novo. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.His1616 amino acid residue in NSD1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12464997). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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