Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000669683 | SCV000794459 | uncertain significance | Non-ketotic hyperglycinemia | 2017-09-26 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000669683 | SCV002307506 | pathogenic | Non-ketotic hyperglycinemia | 2023-12-20 | 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 363 of the AMT protein (p.Gly363Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with glycine encephalopathy (PMID: 27362913; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 554115). 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%. For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003403556 | SCV004122593 | uncertain significance | not specified | 2023-10-09 | criteria provided, single submitter | clinical testing | Variant summary: AMT c.1087G>C (p.Gly363Arg) results in a non-conservative amino acid change located in the Glycine cleavage T-protein, C-terminal barrel domain (IPR013977) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251358 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1087G>C has been reported in the literature in an individual(s) affected with Glycine Encephalopathy (Non-Ketotic Hyperglycinemia) without strong evidence of causality (Coughlin_2017). This report does not provide unequivocal conclusions about association of the variant with Glycine Encephalopathy (Non-Ketotic Hyperglycinemia). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 27362913). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as pathogenic, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Baylor Genetics | RCV000669683 | SCV004194507 | likely pathogenic | Non-ketotic hyperglycinemia | 2023-05-15 | criteria provided, single submitter | clinical testing |