ClinVar Miner

Submissions for variant NM_022455.4(NSD1):c.5927T>C (p.Ile1976Thr) (rs587784167)

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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 RCV000500669 SCV000596110 likely pathogenic Sotos syndrome 1 2016-09-20 criteria provided, single submitter clinical testing
Invitae RCV000805348 SCV000945301 likely pathogenic Beckwith-Wiedemann syndrome 2019-04-12 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 1976 of the NSD1 protein (p.Ile1976Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Sotos syndrome (PMID: 22924495) and it has been observed to be de novo in an individual with features consistent with an NSD1-related condition (Invitae). ClinVar contains an entry for this variant (Variation ID: 436064). 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"). 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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