Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV003231318 | SCV000194257 | pathogenic | Sotos syndrome | 2013-02-08 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003231318 | SCV003332196 | pathogenic | Sotos syndrome | 2022-03-26 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ala2144Glufs*6) in the NSD1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 553 amino acid(s) of the NSD1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NSD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 159420). This variant disrupts a region of the NSD1 protein in which other variant(s) (p.Cys2164Arg) have been determined to be pathogenic (PMID: 15942875; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |