ClinVar Miner

Submissions for variant NM_000170.2(GLDC):c.2521G>C (p.Ala841Pro) (rs386833562)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000049490 SCV000759756 uncertain significance Non-ketotic hyperglycinemia 2017-12-13 criteria provided, single submitter clinical testing This sequence change replaces alanine with proline at codon 841 of the GLDC protein (p.Ala841Pro). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with glycine encephalopathy (PMID: 16601880). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 56081). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049490 SCV000081924 probable-pathogenic Non-ketotic hyperglycinemia no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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