ClinVar Miner

Submissions for variant NM_000170.2(GLDC):c.128del (p.Asp43fs) (rs1251443902)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000667354 SCV000791788 likely pathogenic Non-ketotic hyperglycinemia 2017-05-23 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000667354 SCV000966894 pathogenic Non-ketotic hyperglycinemia 2018-02-07 criteria provided, single submitter clinical testing The p.Asp43AlafsX48 (NM_000170.2 c.128delA) variant in GLDC has been previously reported in 1 compound heterozygous individual with glycine encephalopathy (Swan son 2015), and was absent from large population studies. This variant is predict ed to cause a frameshift, which alters the protein?s amino acid sequence beginni ng at position 43 and leads to a premature termination codon 48 amino acids down stream. This alteration is then predicted to lead to a truncated or absent prote in. Biallelic loss of function of the GLDC gene is associated with glycine encep halopathy. In summary, the p.Asp43AlafsX48 variant meets our criteria to be clas sified as pathogenic for glycine encephalopathy in an autosomal recessive manner based on its occurrence in trans with another pathogenic variant in an affected individual and its predicted impact on the protein.
Invitae RCV000667354 SCV001385089 pathogenic Non-ketotic hyperglycinemia 2019-10-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asp43Alafs*48) in the GLDC gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has been observed as heterozygous in an individual affected with encephalopathy (PMID: 30609409). ClinVar contains an entry for this variant (Variation ID: 552137). Loss-of-function variants in GLDC are known to be pathogenic (PMID: 16601880). For these reasons, this variant has been classified as Pathogenic.

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