Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001985278 | SCV002221969 | uncertain significance | Multiple congenital anomalies-hypotonia-seizures syndrome 1 | 2022-05-15 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 662 of the PIGN protein (p.Leu662Phe). This variant is present in population databases (rs377552386, gnomAD 0.007%). 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: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The phenylalanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV002562929 | SCV003684559 | uncertain significance | Inborn genetic diseases | 2022-01-26 | criteria provided, single submitter | clinical testing | The c.1984C>T (p.L662F) alteration is located in exon 22 (coding exon 19) of the PIGN gene. This alteration results from a C to T substitution at nucleotide position 1984, causing the leucine (L) at amino acid position 662 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |