ClinVar Miner

Submissions for variant NM_022455.4(NSD1):c.6013C>T (p.Arg2005Ter) (rs587784173)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000146902 SCV000194231 pathogenic Sotos syndrome 1 2013-02-08 criteria provided, single submitter clinical testing
GeneDx RCV000255064 SCV000322461 pathogenic not provided 2018-04-05 criteria provided, single submitter clinical testing The R2005X variant in the NSD1 gene has been reported multiple times in association with Sotos syndrome (Turkmen et al., 2003; Tatton-Brown et al., 2005). The R2005X variant is not observed in large population cohorts (Lek et al., 2016). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. We interpret R2005X as a pathogenic variant.
Invitae RCV000699398 SCV000828105 pathogenic Beckwith-Wiedemann syndrome 2019-10-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg2005*) in the NSD1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in an individual affected with Sotos syndrome (PMID: 14571271). This variant has been observed in individuals affected with learning disability, overgrowth, and/or sacrococcygeal teratoma (PMID: 15942875, 28475857). ClinVar contains an entry for this variant (Variation ID: 159394). Loss-of-function variants in NSD1 are known to be pathogenic (PMID: 12464997, 14571271, 15942875, 16247291). For these reasons, this variant has been classified as Pathogenic.
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV000146902 SCV000928345 pathogenic Sotos syndrome 1 2018-02-15 criteria provided, single submitter clinical testing PVS1, PM1, PM2, PP3, PP5

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