ClinVar Miner

Submissions for variant NM_000159.4(GCDH):c.1147C>T (p.Arg383Cys)

gnomAD frequency: 0.00007  dbSNP: rs150938052
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169204 SCV000220457 likely pathogenic Glutaric aciduria, type 1 2014-06-29 criteria provided, single submitter literature only
Invitae RCV000169204 SCV001585091 pathogenic Glutaric aciduria, type 1 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 383 of the GCDH protein (p.Arg383Cys). This variant is present in population databases (rs150938052, gnomAD 0.006%). This missense change has been observed in individual(s) with glutaric aciduria type I (PMID: 15505393, 28438223, 30298489). ClinVar contains an entry for this variant (Variation ID: 188852). 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 80%. This variant disrupts the p.Arg383 amino acid residue in GCDH. Other variant(s) that disrupt this residue have been observed in individuals with GCDH-related conditions (PMID: 15505393, 30203563), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000169204 SCV004199230 pathogenic Glutaric aciduria, type 1 2023-08-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV004017449 SCV004849022 likely pathogenic Inborn genetic diseases 2015-03-25 criteria provided, single submitter clinical testing The c.1147C>T (p.R383C) alteration is located in exon 11 (coding exon 10) of the GCDH gene. This alteration results from a C to T substitution at nucleotide position 1147, causing the arginine (R) at amino acid position 383 to be replaced by a cysteine (C). The heterozygous missense change is ultra rare in healthy individuals:_x000D_ Based on data from the NHLBI Exome Sequencing Project (ESP), the GCDH c.1147C>T alteration was observed in 1 among 13006 total alleles studied (0.01%). Allele frequency data for this nucleotide position are not currently available from the 1000 Genomes Project. This variant is reported in the SNPDatabase as rs150938052. The p.R383 amino acid is conserved throughout available vertebrates. The amino acid is located in a functionally important protein domain:_x000D_ The p.R383C amino acid is located in the acyl-coenzyme A oxidase domain (PLN02526 ). Based on the available evidence, this alteration is classified as likely pathogenic.
Department of Biotechnology and Microbiology, Karnatak University Dharwad RCV000169204 SCV000891777 uncertain significance Glutaric aciduria, type 1 2019-01-03 no assertion criteria provided research
Natera, Inc. RCV000169204 SCV002086992 pathogenic Glutaric aciduria, type 1 2021-08-12 no assertion criteria provided clinical testing

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