ClinVar Miner

Submissions for variant NM_000187.4(HGD):c.8A>C (p.Glu3Ala)

gnomAD frequency: 0.00022  dbSNP: rs200412910
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000671567 SCV000796555 uncertain significance Alkaptonuria 2017-12-28 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000671567 SCV001310176 uncertain significance Alkaptonuria 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Fulgent Genetics, Fulgent Genetics RCV000671567 SCV002786351 uncertain significance Alkaptonuria 2022-02-11 criteria provided, single submitter clinical testing
Invitae RCV000671567 SCV003290355 uncertain significance Alkaptonuria 2022-07-16 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 3 of the HGD protein (p.Glu3Ala). This variant is present in population databases (rs200412910, gnomAD 0.07%). This missense change has been observed in individual(s) with alkaptonuria (PMID: 19862842). ClinVar contains an entry for this variant (Variation ID: 555702). 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 not expected to disrupt HGD protein function. 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.
Department Of Human Genetics, Institute Of Clinical And Translational Research, Biomedical Research Center, Slovak Academy Of Sciences RCV000671567 SCV004101011 pathogenic Alkaptonuria no assertion criteria provided research The variant was originally described in AKU patient in PMID:19862842. It has been submitted to the HGD gene mutation database (, DB-ID: AKU_00001).

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