ClinVar Miner

Submissions for variant NM_002641.4(PIGA):c.356G>A (p.Arg119Gln)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Génétique des Maladies du Développement, Hospices Civils de Lyon RCV001004672 SCV001164125 likely pathogenic Multiple congenital anomalies-hypotonia-seizures syndrome 2 2017-01-26 criteria provided, single submitter clinical testing
GeneDx RCV001552602 SCV001773314 likely pathogenic not provided 2020-02-05 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 32694024, 32452540, 32220244, 29310717, 29656098, 26633542, 31704190, 31618474)
Revvity Omics, Revvity RCV001552602 SCV002024619 likely pathogenic not provided 2019-12-17 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001004672 SCV004014732 pathogenic Multiple congenital anomalies-hypotonia-seizures syndrome 2 2023-01-03 criteria provided, single submitter clinical testing The PIGA c.356G>A (p.Arg119Gln) missense variant results in the substitution of arginine at amino acid position 119 with glutamine. This variant has been reported in a hemizygous state in at least seven affected male individuals presenting with a spectrum of epilepsy and developmental delay (PMID: 32452540; PMID: 29656098; PMID: 32220244; PMID: 32694024; PMID: 31618474; PMID: 33508693). A variant resulting in a different amino acid change at the same position, c.355C>T (p.Arg119Trp), has been reported in a hemizygous state in four males with the same phenotype spectrum of disease (PMID: 32452540; PMID: 24706016; PMID: 31175295). The c.356G>A variant is not found in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. The variant lies, along with the majority of pathogenic missense variants, within the Rossmann fold A of the N-terminal cytoplasmic domain (PMID: 32452540). Based on the available evidence, the c.356G>A (p.Arg119Gln) variant is classified as pathogenic for PIGA-related congenital disorder of glycosylation.
PreventionGenetics, part of Exact Sciences RCV003983820 SCV004800448 pathogenic PIGA-related condition 2024-01-31 criteria provided, single submitter clinical testing The PIGA c.356G>A variant is predicted to result in the amino acid substitution p.Arg119Gln. This variant was reported in at least six unrelated individuals with PIGA-associated disorders (Lin et al. 2018. PubMed ID: 29656098; Table S2, Knaus et al. 2018. PubMed ID: 29310717; Table S2, Burgess et al. 2019. PubMed ID: 31618474; Jiao et al. 2020. PubMed ID: 32220244; Bayat et al. 2020. PubMed ID: 32452540). This variant has not been reported in a large population database, indicating this variant is rare. A different nucleotide substitution affecting the same amino acid (p.Arg119Trp) has been reported in individuals with early-onset epileptic encephalopathy (Kato et al. 2014. PubMed ID: 24706016; Bayat et al. 2020. PubMed ID: 32452540). Taken together, the c.356G>A (p.Arg119Gln) variant is interpreted as pathogenic.

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