ClinVar Miner

Submissions for variant NM_002074.5(GNB1):c.388G>A (p.Glu130Lys)

dbSNP: rs1553194155
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523422 SCV000621634 pathogenic not provided 2024-09-23 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV002470899 SCV002769439 pathogenic Intellectual disability, autosomal dominant 42 2021-05-06 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 a suggested mechanism of disease in this gene and is associated with GNB1-related neurodevelopmental disorder (MIM#616973). However, a dominant-negative disease mechanism has not been excluded (PMID: 28087732, 32918542). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Phenotypes reported to have variability include epilepsy/seizures and brain abnormalities (PMID: 32918542). (I) 0200 - Variant is predicted to result in a missense amino acid change from glutamic acid to lysine. (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 uninformative 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) 0803 - This variant has limited previous evidence of pathogenicity. It is reported once as likely pathogenic in ClinVar. (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) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP)

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