ClinVar Miner

Submissions for variant NM_000170.2(GLDC):c.2311G>A (p.Gly771Arg) (rs386833553)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000049481 SCV000791590 likely pathogenic Non-ketotic hyperglycinemia 2017-05-17 criteria provided, single submitter clinical testing
Invitae RCV000049481 SCV000636381 pathogenic Non-ketotic hyperglycinemia 2017-07-19 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 771 of the GLDC protein (p.Gly771Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed on the opposite chromosome (in trans) from another pathogenic variant in an individual affected with nonketotic hyperglycinemia (PMID: 27362913). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. It has also been reported to co-occur with other GLDC variants in several other affected individuals (PMID: 16450403, 17361008, 27362913), with one allele having arisen de novo (PMID: 27362913). ClinVar contains an entry for this variant (Variation ID: 56072). 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: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049481 SCV000081915 probable-pathogenic Non-ketotic hyperglycinemia no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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