Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001033644 | SCV001196951 | pathogenic | Marshall-Smith syndrome; Malan overgrowth syndrome | 2019-02-23 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 9-11 of the NFIX gene. The 5' boundary is likely confined to intron 8. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. This variant has been observed in an individual affected with Sotos syndrome (Invitae). This variant disrupts the C-terminus of the NFIX protein. Other variant(s) that disrupt this region (p.Arg494Glyfs*6, also known as p.R486Gfs*6) have been determined to be pathogenic (PMID:24924640). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. |