ClinVar Miner

Submissions for variant NM_005859.5(PURA):c.596G>C (p.Arg199Pro)

dbSNP: rs587783001
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000656234 SCV000815080 likely pathogenic PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome 2017-09-15 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been reported to be de novo an individual affected with seizures, hypotonia and feeding difficulties (PMID: 25439098). ClinVar contains an entry for this variant (Variation ID: 156413). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with proline at codon 199 of the PURA protein (p.Arg199Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline.
Laboratoire de Génétique Moléculaire, CHU Bordeaux RCV001281647 SCV001468987 pathogenic not provided criteria provided, single submitter clinical testing
GeneDx RCV001281647 SCV001820929 pathogenic not provided 2020-01-29 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 29150892, 25439098)
Whole genome laboratory; Baylor College of Medicine RCV000144531 SCV000189123 pathogenic Global developmental delay; Seizure; Delayed speech and language development; Intellectual disability; Neonatal hypotonia 2014-09-15 no assertion criteria provided clinical testing
GeneReviews RCV000656234 SCV000778187 not provided PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome no assertion provided literature only

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