Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV005234271 | SCV005878986 | pathogenic | Sotos syndrome | 2024-04-19 | criteria provided, single submitter | clinical testing | The NSD1 c.3345_3348del; p.Lys1115AsnfsTer25 variant, to our knowledge, is not reported in the medical literature or gene specific databases. This variant is also absent from the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. This variant causes a frameshift by deleting four nucleotides in exon 5 of 23, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Loss-of-function variants in the NSD1 gene, including those located in exon 5, are a known mechanism of disease (see Tatton-Brown 2005). Based on available information, this variant is considered to be pathogenic. References: Tatton-Brown K et al. Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations. Am J Hum Genet. 2005 Aug;77(2):193-204. PMID: 15942875. |