ClinVar Miner

Submissions for variant NM_198903.2(GABRG2):c.964C>T (p.Pro322Ser) (rs796052508)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute for Genomic Medicine (IGM) Clinical Laboratory,Nationwide Children's Hospital RCV001249644 SCV001423657 pathogenic Epilepsy, childhood absence 2; Developmental and epileptic encephalopathy, 74 2017-11-16 criteria provided, single submitter clinical testing [ACMG/AMP: PS2, PS3, PM2, PM5, PP2, PP3, PP5] This alteration is de novo in origin as it was not detected in the submitted parental specimens (identity confirmed) [PS2], is supported by well-established in vitro or in vivo functional studies to have a damaging effect on protein function or splicing [PS3], is absent from or rarely observed in large-scale population databases [PM2], is a novel missense change at an amino residue where a different missense change has been deemed to be pathogenic [PM5], is a missense variant in a gene in which missense variants are a common mechanism of disease [PP2], is predicted to be damaging by multiple functional prediction tools [PP3], was reported as a pathogenic/likely pathogenic alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory) [PP5].
Invitae RCV001390804 SCV001592652 pathogenic Epilepsy, childhood absence 2; Familial febrile seizures 8 2020-08-10 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 282 of the GABRG2 protein (p.Pro282Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with epileptic encephalopathy (PMID: 27864268). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 625863). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GABRG2 protein function. Experimental studies have shown that this variant affects GABRG2 protein function (PMID: 27864268). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000767870 SCV000898482 pathogenic Developmental and epileptic encephalopathy, 74 2020-11-25 no assertion criteria provided literature only

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