ClinVar Miner

Submissions for variant NM_022455.4(NSD1):c.4417C>T (p.Arg1473Ter) (rs587784117)

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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 RCV000146834 SCV000194163 pathogenic Sotos syndrome 1 2013-02-08 criteria provided, single submitter clinical testing
GeneDx RCV000492820 SCV000582371 pathogenic not provided 2015-09-13 criteria provided, single submitter clinical testing The R1473X variant in the NSD1 gene has been reported previously as a de novo variant in a patient with Sotos syndrome (Douglas et al., 2003). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Furthermore, R1473X was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, we interpret R1473X as a pathogenic variant.
Invitae RCV000628542 SCV000749444 pathogenic Beckwith-Wiedemann syndrome 2018-01-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1473*) 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 in several individuals affected with overgrowth and intellectual disability (PMID: 28475857) and has been reported to be de novo in at least one individual affected with Sotos syndrome (PMID: 12464997). ClinVar contains an entry for this variant (Variation ID: 159331). 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.

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