ClinVar Miner

Submissions for variant NM_000170.2(GLDC):c.2293C>T (p.Pro765Ser) (rs386833551)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000419990 SCV000520834 likely pathogenic not provided 2016-11-29 criteria provided, single submitter clinical testing The P765S variant in the GLDC gene has been reported previously in one individual with neonatalnonketotic hyperglycinemia, although a second GLDC pathogenic variant was not identified in thisindividual (Kure et al., 2006). This variant was not observed in approximately 6500 individuals ofEuropean and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is nota common benign variant in these populations. The P765S variant is a non-conservative amino acidsubstitution, which is likely to impact secondary protein structure as these residues differ in polarity,charge, size and/or other properties. This substitution occurs at a position that is conserved acrossspecies, and in silico analysis predicts this variant is probably damaging to the proteinstructure/function. Missense variants in nearby residues (H760Q, G761R, G762R, G766C, P769L)have been reported in the Human Gene Mutation Database in association with nonketotichyperglycinemia (Stenson et al., 2014), supporting the functional importance of this region of theprotein.The P765S variant is a strong candidate for a pathogenic variant.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049479 SCV000081913 probable-pathogenic Non-ketotic hyperglycinemia no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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