Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001364599 | SCV001560756 | uncertain significance | Multiple congenital anomalies-hypotonia-seizures syndrome 2 | 2022-09-07 | criteria provided, single submitter | clinical testing | 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: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1055858). This missense change has been observed in individual(s) with clinical features of PIGA-related conditions (Invitae). This variant is present in population databases (rs752395232, gnomAD 0.001%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 173 of the PIGA protein (p.Val173Met). |
Illumina Laboratory Services, |
RCV001364599 | SCV002038575 | uncertain significance | Multiple congenital anomalies-hypotonia-seizures syndrome 2 | 2021-06-08 | criteria provided, single submitter | clinical testing | The PIGA c.517G>A (p.Val173Met) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is found at a frequency of 0.000048 in the European (Non-Finnish) population of the Genome Aggregation Database (version 3.1.1), though this is based on two heterozygous alleles in a region of good sequence coverage so the variant is presumed to be rare. Based on the available evidence, the p.Val173Met variant is classified as a variant of uncertain significance for multiple congenital anomalies-hypotonia-seizures syndrome 2. |
Ambry Genetics | RCV002341772 | SCV002643142 | uncertain significance | Inborn genetic diseases | 2017-10-27 | criteria provided, single submitter | clinical testing | The p.V173M variant (also known as c.517G>A), located in coding exon 1 of the PIGA gene, results from a G to A substitution at nucleotide position 517. The valine at codon 173 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly 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. |