ClinVar Miner

Submissions for variant NM_000159.4(GCDH):c.1298C>T (p.Ala433Val)

gnomAD frequency: 0.00002  dbSNP: rs933624223
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000672203 SCV002173332 pathogenic Glutaric aciduria, type 1 2024-03-27 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 433 of the GCDH protein (p.Ala433Val). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with glutaric acidemia type I (PMID: 10960496, 21176883, 29201125, 31952437). ClinVar contains an entry for this variant (Variation ID: 556228). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects GCDH function (PMID: 12948740). This variant disrupts the p.Ala433 amino acid residue in GCDH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9600243). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000672203 SCV002516346 likely pathogenic Glutaric aciduria, type 1 2022-05-04 criteria provided, single submitter clinical testing
Baylor Genetics RCV000672203 SCV004199198 likely pathogenic Glutaric aciduria, type 1 2024-02-27 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000672203 SCV005655083 likely pathogenic Glutaric aciduria, type 1 2024-02-10 criteria provided, single submitter clinical testing
Counsyl RCV000672203 SCV000797284 uncertain significance Glutaric aciduria, type 1 2018-01-19 flagged submission clinical testing

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