ClinVar Miner

Submissions for variant NM_002641.4(PIGA):c.517G>A (p.Val173Met)

gnomAD frequency: 0.00002  dbSNP: rs752395232
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Total submissions: 3
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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, Illumina 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.

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