ClinVar Miner

Submissions for variant NM_022455.4(NSD1):c.6454C>T (p.Arg2152Ter) (rs587784199)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory,University of Chicago RCV000146930 SCV000194259 pathogenic Sotos syndrome 1 2013-02-08 criteria provided, single submitter clinical testing
GeneDx RCV000394674 SCV000329443 pathogenic not provided 2015-08-12 criteria provided, single submitter clinical testing The R2152X nonsense mutation in the NSD1 gene has been reported previously in association with Sotos syndrome (Tong et al., 2005; Tatton-Brown et al., 2005). It is predicted to cause loss of normal protein function through protein truncation, specifically with the loss of the last 545 amino acid residues of the protein.
Invitae RCV000628531 SCV000749433 pathogenic Beckwith-Wiedemann syndrome 2019-04-09 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the NSD1 gene (p.Arg2152*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 545 amino acids of the NSD1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with Sotos syndrome (PMID: 15942875, 27604501, 16247291). This variant has also been reported in the literature as c.5647C>T (p.Arg1883*) based on an alternative transcript (NM_172349.2). ClinVar contains an entry for this variant (Variation ID: 159421). Different truncations (p.Gln2163*, p.Arg2187*, p.Glu2505Glyfs*73) that lie downstream of this variant has been determined to be pathogenic (PMID: 16247291, 15742365, Invitae). This suggests that deletion of this region of the NSD1 protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.

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