Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000484035 | SCV000574262 | uncertain significance | not provided | 2017-03-29 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the PIGA gene. The I206V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. A different missense substitution at the same residue (I206F) has been previously reported as a maternally inherited variant in a male with West syndrome (Kato et al. 2014). The I206V variant is observed in 1/9319 (0.01%) alleles from individuals of Latino background, (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is conserved across species. However, the I206V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Ambry Genetics | RCV002318585 | SCV000851206 | uncertain significance | Inborn genetic diseases | 2016-09-13 | criteria provided, single submitter | clinical testing | The p.I206V variant (also known as c.616A>G), located in coding exon 1 of the PIGA gene, results from an A to G substitution at nucleotide position 616. The isoleucine at codon 206 is replaced by valine, an amino acid with highly similar properties. Another variant at the same amino acid position (p.I206F) has been reported in a patient diagnosed with West syndrome with hypomyelination (Kato M et al. Neurology, 2014 May;82:1587-96). The p.I206V variant was previously reported in the SNPDatabase as rs201119959. Based on data from the 1000 Genomes Project, the G allele has an overall frequency of approximately 0% (0/503) total male alleles studied. In the NHLBI Exome Sequencing Project (ESP), this variant was not observed in 6503 samples with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV002525974 | SCV003008286 | likely benign | Multiple congenital anomalies-hypotonia-seizures syndrome 2 | 2022-11-03 | criteria provided, single submitter | clinical testing |