Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000482884 | SCV000570692 | likely pathogenic | not provided | 2016-06-14 | criteria provided, single submitter | clinical testing | The P191L variant in the PURA gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P191L variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P191L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, we interpret P191L as a likely pathogenic variant. |
| Ambry Genetics | RCV001265745 | SCV001443914 | likely pathogenic | Inborn genetic diseases | 2019-03-18 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV002267612 | SCV002549753 | pathogenic | PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome due to a point mutation | 2022-06-24 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is likely a mechanism of disease in this gene and is associated with neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (MIM#616158; PMID: 28448108). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity (PMID: 29097605). (I) 0200 - Variant is predicted to result in a missense amino acid change from proline to leucine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and high conservation. (I) 0603 - Missense variant in a region that is highly intolerant to missense variation (high constraint region in DECIPHER). (SP) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been classified as likely pathogenic by two clinical laboratories in ClinVar and observed as de novo in an individual with severe intellectual disability (DECIPHER, PMID: 29097605). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |