ClinVar Miner

Submissions for variant NM_000159.4(GCDH):c.150G>C (p.Trp50Cys)

dbSNP: rs1970564149
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001066989 SCV001232015 pathogenic Glutaric aciduria, type 1 2023-02-22 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with glutaric acidemia type 1 (PMID: 28062662; Invitae). This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 50 of the GCDH protein (p.Trp50Cys). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 860645). 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. Experimental studies have shown that this missense change affects GCDH function (PMID: 28062662). This variant disrupts the p.Trp50 amino acid residue in GCDH. Other variant(s) that disrupt this residue have been observed in individuals with GCDH-related conditions (PMID: 21811973, 29665094), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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