Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute for Genomic Medicine |
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]. |
Labcorp Genetics |
RCV001390804 | SCV001592652 | pathogenic | Epilepsy, childhood absence 2; Febrile seizures, familial, 8 | 2022-12-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GABRG2 function (PMID: 27864268). 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. ClinVar contains an entry for this variant (Variation ID: 625863). This variant is also known as c.964C>T p.Pro322Ser. This missense change has been observed in individual(s) with clinical features of epileptic encephalopathy (PMID: 27864268, 31785789, 32371413). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 282 of the GABRG2 protein (p.Pro282Ser). |
OMIM | RCV000767870 | SCV000898482 | pathogenic | Developmental and epileptic encephalopathy, 74 | 2020-11-25 | no assertion criteria provided | literature only |