ClinVar Miner

Submissions for variant NM_000159.4(GCDH):c.460G>A (p.Ala154Thr)

gnomAD frequency: 0.00001  dbSNP: rs759415410
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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 RCV001360891 SCV001556847 uncertain significance Glutaric aciduria, type 1 2022-07-12 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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: 1052666). This variant has not been reported in the literature in individuals affected with GCDH-related conditions. This variant is present in population databases (rs759415410, gnomAD 0.01%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 154 of the GCDH protein (p.Ala154Thr).
GeneDx RCV002293531 SCV002586756 uncertain significance not provided 2022-04-22 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002341759 SCV002637755 uncertain significance Inborn genetic diseases 2024-02-26 criteria provided, single submitter clinical testing The c.460G>A (p.A154T) alteration is located in exon 6 (coding exon 5) of the GCDH gene. This alteration results from a G to A substitution at nucleotide position 460, causing the alanine (A) at amino acid position 154 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003416261 SCV004117635 uncertain significance GCDH-related disorder 2023-01-30 criteria provided, single submitter clinical testing The GCDH c.460G>A variant is predicted to result in the amino acid substitution p.Ala154Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-13004422-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Natera, Inc. RCV001360891 SCV002086965 uncertain significance Glutaric aciduria, type 1 2019-12-10 no assertion criteria provided clinical testing

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