Submissions for variant NM_000481.4(AMT):c.173C>T (p.Pro58Leu)

gnomAD frequency: 0.00001  dbSNP: rs1008341193

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001248283	SCV001421756	uncertain significance	Glycine encephalopathy	2022-07-12	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 58 of the AMT protein (p.Pro58Leu). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with AMT-related conditions. ClinVar contains an entry for this variant (Variation ID: 972290). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV001248283	SCV003807716	uncertain significance	Glycine encephalopathy	2022-07-05	criteria provided, single submitter	clinical testing	ACMG classification criteria: PM2 moderated, PP3 supporting, PP4
Natera, Inc.	RCV001248283	SCV001467334	uncertain significance	Glycine encephalopathy	2020-08-13	no assertion criteria provided	clinical testing