ClinVar Miner

Submissions for variant NM_022455.4(NSD1):c.5714G>C (p.Cys1905Ser) (rs1554204110)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523134 SCV000621196 uncertain significance not provided 2017-09-28 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the NSD1 gene. The C1905S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The C1905S variant is not observed in large population cohorts (Lek et al., 2016). The C1905S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species; and in silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV001048565 SCV001212578 likely pathogenic Beckwith-Wiedemann syndrome 2019-12-30 criteria provided, single submitter clinical testing This sequence change replaces cysteine with serine at codon 1905 of the NSD1 protein (p.Cys1905Ser). The cysteine residue is highly conserved and there is a moderate physicochemical difference between cysteine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Sotos syndrome (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 452389). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.