Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002354150 | SCV002649569 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-17 | criteria provided, single submitter | clinical testing | The p.G197D variant (also known as c.590G>A), located in coding exon 3 of the PHOX2B gene, results from a G to A substitution at nucleotide position 590. The glycine at codon 197 is replaced by aspartic acid, an amino acid with similar properties. This alteration was reported in a 5-year-old female diagnosed with a metastatic adrenal neuroblastoma and thoracic ganglioneuroblastoma, and was also detected in her father, who was diagnosed with a ganglioneuroblastoma. Family history included three additional individuals with neural crest tumors (McConville C et al. Am. J. Med. Genet. A 2006 Jun;140(12):1297-301). One in vitro functional study showed that transactivation activity of PHOX2B p.G197D was similar to wild-type (Trochet D Hum. Mutat. 2009 Feb;30(2):E421-31). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| OMIM | RCV000006385 | SCV000026567 | risk factor | Neuroblastoma, susceptibility to, 2 | 2006-06-15 | no assertion criteria provided | literature only |