ClinVar Miner

Submissions for variant NM_022455.5(NSD1):c.5685C>G (p.Cys1895Trp)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001064657 SCV001229569 likely pathogenic Beckwith-Wiedemann syndrome 2019-12-05 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tryptophan at codon 1895 of the NSD1 protein (p.Cys1895Trp). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Sotos syndrome (PMID: 15942875, 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.Cys1895 amino acid residue in NSD1. Other variant(s) that disrupt this residue have been observed in individuals with NSD1-related conditions (PMID: 14517949), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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