Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003232230 | SCV001379880 | pathogenic | Sotos syndrome | 2021-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine with tyrosine at codon 1895 of the NSD1 protein (p.Cys1895Tyr). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with clinical features of Sotos syndrome (PMID: 14517949; Invitae). In at least one individual the variant was observed to be de novo. 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"). This variant disrupts the p.Cys1895 amino acid residue in NSD1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15942875; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |