ClinVar Miner

Submissions for variant NM_000481.4(AMT):c.664C>T (p.Arg222Cys) (rs781466698)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668200 SCV000792762 likely pathogenic Non-ketotic hyperglycinemia 2017-07-12 criteria provided, single submitter clinical testing
Invitae RCV000668200 SCV000962354 pathogenic Non-ketotic hyperglycinemia 2019-10-07 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 222 of the AMT protein (p.Arg222Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs781466698, ExAC 0.003%). This variant has been observed to be homozygous or in combination with another AMT variant in several individuals and a family affected with glycine encephalopathy (PMID: 25231368, 26179960, 27362913). ClinVar contains an entry for this variant (Variation ID: 552860). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.

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