ClinVar Miner

Submissions for variant NM_000170.2(GLDC):c.2919+1G>C

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000795305 SCV000934760 pathogenic Non-ketotic hyperglycinemia 2018-09-21 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in the last intron (intron 24) of the GLDC gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (ExAC no frequency). Variants at this nucleotide position (c.2919+1G) have been observed on the opposite chromosome (in trans) from a pathogenic variant in individuals affected with glycine encephalopathy (PMID: 26179960, 16601880). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.

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