Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000691638 | SCV000819424 | uncertain significance | Multiple congenital anomalies-hypotonia-seizures syndrome 1 | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with serine at codon 549 of the PIGN protein (p.Leu549Ser). The leucine residue is moderately conserved and there is a large physicochemical difference between leucine and serine. This variant is present in population databases (rs769428343, ExAC 0.4%). 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 output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 | RCV003279002 | SCV003959169 | uncertain significance | Inborn genetic diseases | 2023-05-18 | criteria provided, single submitter | clinical testing | The c.1646T>C (p.L549S) alteration is located in exon 18 (coding exon 15) of the PIGN gene. This alteration results from a T to C substitution at nucleotide position 1646, causing the leucine (L) at amino acid position 549 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |