ClinVar Miner

Submissions for variant NM_020988.3(GNAO1):c.470T>C (p.Leu157Pro)

dbSNP: rs2143660403
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV004594270 SCV005086943 pathogenic Developmental and epileptic encephalopathy, 17 2023-07-16 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: 0103 - Both loss- and gain-of-function are known mechanisms of disease for this gene. Loss of function variants are found throughout the protein, and result in developmental and epileptic encephalopathy 17 (MIM#615473). Gain of function variants cluster near amino acid 184 and within the RGS binding domain, causing a neurodevelopmental disorder with involuntary movements (MIM#617493) (PMID: 28747448, OMIM). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from leucine to proline. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated G-alpha domain (PMID: 34122306). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported as de novo in at least two individuals, with features including early infantile epileptic encephalopathy with movement disorder, or severe global developmental delay with seizures, strabismus and hypotonia (ClinVar, DECIPHER). (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
Pediatric Department, Peking University First Hospital RCV001580367 SCV001486213 likely pathogenic Developmental and epileptic encephalopathy, 17; Neurodevelopmental disorder with involuntary movements 2021-02-03 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.