Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002038726 | SCV002309394 | uncertain significance | Multiple congenital anomalies-hypotonia-seizures syndrome 1 | 2021-09-15 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with serine at codon 196 of the PIGN protein (p.Phe196Ser). The phenylalanine residue is moderately conserved and there is a large physicochemical difference between phenylalanine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with PIGN-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 | RCV002352769 | SCV002651809 | uncertain significance | Inborn genetic diseases | 2017-06-30 | criteria provided, single submitter | clinical testing | The p.F196S variant (also known as c.587T>C), located in coding exon 5 of the PIGN gene, results from a T to C substitution at nucleotide position 587. The phenylalanine at codon 196 is replaced by serine, 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. |