ClinVar Miner

Submissions for variant NM_000481.4(AMT):c.217C>T (p.Arg73Cys) (rs386833679)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000049640 SCV000636425 likely pathogenic Non-ketotic hyperglycinemia 2019-09-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 73 of the AMT protein (p.Arg73Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs386833679, ExAC 0.01%). This variant has been observed in several individuals affected with glycine encephalopathy, including on the opposite chromosome (in trans) from a pathogenic variant in one of them (PMID: 16450403, 27362913, Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001090584 SCV001246198 pathogenic not provided 2020-04-01 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001196963 SCV001367597 likely pathogenic Seizures 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: PVS1,PM2. This variant was detected in heterozygous state.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) 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

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