ClinVar Miner

Submissions for variant NM_000170.2(GLDC):c.2798T>C (p.Ile933Thr) (rs758029533)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000666803 SCV000791159 uncertain significance Non-ketotic hyperglycinemia 2017-05-01 criteria provided, single submitter clinical testing
Invitae RCV000666803 SCV001202309 pathogenic Non-ketotic hyperglycinemia 2019-11-18 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 933 of the GLDC protein (p.Ile933Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs758029533, ExAC 0.009%). This variant has been observed to be homozygous or in combination with another GLDC variant in individual(s) with glycine encephalopathy (PMID: 26179960, 27362913). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 551679). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Ile933 amino acid residue in GLDC. Other variant(s) that disrupt this residue have been observed in individuals with GLDC-related conditions (PMID: 27362913), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001092996 SCV001249760 pathogenic not provided 2016-10-01 criteria provided, single submitter clinical testing

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