Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002611228 | SCV003504708 | uncertain significance | Haddad syndrome | 2022-03-28 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 249 of the PHOX2B protein (p.Ala249Ser). This variant is not present in population databases (gnomAD no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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: "Not Available"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with PHOX2B-related conditions. |
| Baylor Genetics | RCV003475514 | SCV004203999 | uncertain significance | Neuroblastoma, susceptibility to, 2 | 2023-02-27 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004661582 | SCV005147640 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-27 | criteria provided, single submitter | clinical testing | The p.A249S variant (also known as c.745G>T), located in coding exon 3 of the PHOX2B gene, results from a G to T substitution at nucleotide position 745. The alanine at codon 249 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |