Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000622444 | SCV000741346 | uncertain significance | Inborn genetic diseases | 2016-03-04 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000012755 | SCV000827129 | pathogenic | Non-ketotic hyperglycinemia | 2023-11-20 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 47 of the AMT protein (p.Gly47Arg). This variant is present in population databases (rs121964982, gnomAD 0.009%). This missense change has been observed in individual(s) with glycine encephalopathy (PMID: 8005589, 27362913; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 11975). 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 AMT protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects AMT function (PMID: 23352163). For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV000012755 | SCV004196246 | likely pathogenic | Non-ketotic hyperglycinemia | 2023-08-29 | criteria provided, single submitter | clinical testing | |
OMIM | RCV003230354 | SCV000032990 | pathogenic | Glycine encephalopathy 2 | 1994-06-01 | no assertion criteria provided | literature only |