Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001035688 | SCV001199022 | uncertain significance | Haddad syndrome | 2020-10-19 | criteria provided, single submitter | clinical testing | 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: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with PHOX2B-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces glycine with cysteine at codon 240 of the PHOX2B protein (p.Gly240Cys). The glycine residue is moderately conserved and there is a large physicochemical difference between glycine and cysteine. 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. |
| Ambry Genetics | RCV002372743 | SCV002672310 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-10-19 | criteria provided, single submitter | clinical testing | The p.G240C variant (also known as c.718G>T), located in coding exon 3 of the PHOX2B gene, results from a G to T substitution at nucleotide position 718. The glycine at codon 240 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |