ClinVar Miner

Submissions for variant NM_000170.2(GLDC):c.2323C>T (p.His775Tyr) (rs1554643619)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000638271 SCV000759760 likely pathogenic Non-ketotic hyperglycinemia 2018-04-18 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 775 of the GLDC protein (p.His775Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with biochemical findings that are highly specific for glycine encephalopathy (Invitae). 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Two additional missense substitution at this codon (p.His775Arg, p.His775Pro) have been reported in trans with pathogenic variants in the GLDC gene in individuals affected with glycine encephalopathy (PMID: 16601880, 27362913). This suggests that the histidine residue is critical for GLDC protein function. 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.

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