Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000049640 | SCV000636425 | pathogenic | Non-ketotic hyperglycinemia | 2023-12-21 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 73 of the AMT protein (p.Arg73Cys). This variant is present in population databases (rs386833679, gnomAD 0.006%). This missense change has been observed in individual(s) with glycine encephalopathy (PMID: 16450403, 27362913). 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: 56228). 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. |
Ce |
RCV001090584 | SCV001246198 | pathogenic | not provided | 2023-09-01 | criteria provided, single submitter | clinical testing | AMT: PM3:Very Strong, PM2 |
Centre for Mendelian Genomics, |
RCV000049640 | SCV001367597 | likely pathogenic | Non-ketotic hyperglycinemia | 2020-04-02 | criteria provided, single submitter | clinical testing | This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PM3_STR,PM2,PP3. |
Centre for Inherited Metabolic Diseases, |
RCV000049640 | SCV001502669 | pathogenic | Non-ketotic hyperglycinemia | 2021-03-12 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000049640 | SCV002050700 | pathogenic | Non-ketotic hyperglycinemia | 2021-12-01 | criteria provided, single submitter | clinical testing | Variant summary: AMT c.217C>T (p.Arg73Cys) results in a non-conservative amino acid change located in the Aminomethyltransferase, folate-binding domain (IPR006222) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-05 in 251240 control chromosomes (gnomAD). c.217C>T has been reported in the literature in multiple compound heterozygous and homozygous individuals affected with Glycine Encephalopathy (Non-Ketotic Hyperglycinemia) (example: Kure_2006, Coughlin_2017, Isik_2019, Stranneheim_2021). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six ClinVar submitters have assessed this variant after 2014: four classified the variant as likely pathogenic and two have classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Laboratorio de Genetica e Diagnostico Molecular, |
RCV002251953 | SCV002523424 | likely pathogenic | See cases | 2019-12-26 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PS4, PM2, PM3, PP3 |
Baylor Genetics | RCV000049640 | SCV004196279 | likely pathogenic | Non-ketotic hyperglycinemia | 2023-07-10 | criteria provided, single submitter | clinical testing | |
Juha Muilu Group; Institute for Molecular Medicine Finland |
RCV000049640 | SCV000082047 | probable-pathogenic | Non-ketotic hyperglycinemia | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. | |
Counsyl | RCV000049640 | SCV000790201 | likely pathogenic | Non-ketotic hyperglycinemia | 2017-03-17 | no assertion criteria provided | clinical testing | |
Natera, |
RCV000049640 | SCV001460430 | likely pathogenic | Non-ketotic hyperglycinemia | 2020-09-16 | no assertion criteria provided | clinical testing |