ClinVar Miner

Submissions for variant NM_002641.4(PIGA):c.1234C>T (p.Arg412Ter)

dbSNP: rs387906726
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001007979 SCV001167711 pathogenic not provided 2020-09-02 criteria provided, single submitter clinical testing Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 73 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 23561846, 24784135, 22305531, 32562213, 28441409, 24706016, 26545172, 31704190, 32256299)
Invitae RCV000022881 SCV001217804 pathogenic Multiple congenital anomalies-hypotonia-seizures syndrome 2 2023-01-11 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this premature translational stop signal affects PIGA function (PMID: 22305531, 28441409). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 29988). This premature translational stop signal has been observed in individuals with PIGA-related multiple congenital anomalies-hypotonia-seizures syndrome (PMID: 22305531, 24706016, 26545172). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg412*) in the PIGA gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 73 amino acid(s) of the PIGA protein.
CeGaT Center for Human Genetics Tuebingen RCV001007979 SCV001250207 pathogenic not provided 2018-06-01 criteria provided, single submitter clinical testing
OMIM RCV000022881 SCV000044172 pathogenic Multiple congenital anomalies-hypotonia-seizures syndrome 2 2014-05-06 no assertion criteria provided literature only
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City RCV000022881 SCV001190768 pathogenic Multiple congenital anomalies-hypotonia-seizures syndrome 2 2020-02-05 no assertion criteria provided clinical testing

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