Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000670173 | SCV000794999 | uncertain significance | Glycine encephalopathy | 2017-10-24 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000670173 | SCV002285270 | likely pathogenic | Glycine encephalopathy | 2021-08-08 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with asparagine at codon 995 of the GLDC protein (p.Asp995Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 GLDC protein function. ClinVar contains an entry for this variant (Variation ID: 554525). This missense change has been observed in individual(s) with nonketotic hyperglycinemia (PMID: 27362913). This variant is not present in population databases (ExAC no frequency). |