ClinVar Miner

Submissions for variant NM_000159.4(GCDH):c.148T>G (p.Trp50Gly)

gnomAD frequency: 0.00001  dbSNP: rs758646992
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001563484 SCV001786435 likely pathogenic not provided 2020-04-14 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29665094)
Labcorp Genetics (formerly Invitae), Labcorp RCV001832767 SCV004539066 pathogenic Glutaric aciduria, type 1 2022-12-03 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Trp50 amino acid residue in GCDH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 28062662; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GCDH protein function. ClinVar contains an entry for this variant (Variation ID: 1199104). This missense change has been observed in individual(s) with glutaric acidemia (PMID: 29665094). This variant is present in population databases (rs758646992, gnomAD 0.009%). This sequence change replaces tryptophan, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 50 of the GCDH protein (p.Trp50Gly).
Natera, Inc. RCV001832767 SCV002086955 likely pathogenic Glutaric aciduria, type 1 2021-10-15 no assertion criteria provided clinical testing

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