ClinVar Miner

Submissions for variant NM_022455.4(NSD1):c.6356A>G (p.Asp2119Gly) (rs587784191)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000146921 SCV000194250 pathogenic Sotos syndrome 1 2013-02-08 criteria provided, single submitter clinical testing
Invitae RCV000820630 SCV000961349 likely pathogenic Beckwith-Wiedemann syndrome 2018-09-04 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 2119 of the NSD1 protein (p.Asp2119Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual with clinical features of Sotos syndrome (Invitae). This variant has been observed in several individuals with clinical features of Sotos syndrome (PMID: 16247291, 22924495). ClinVar contains an entry for this variant (Variation ID: 159413). 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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