ClinVar Miner

Submissions for variant NM_000187.4(HGD):c.566G>T (p.Ser189Ile)

dbSNP: rs2107510544
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
NxGen MDx RCV001376105 SCV001573121 likely pathogenic Alkaptonuria 2019-12-30 criteria provided, single submitter clinical testing This sequence change (c.566G>T) on exon 9 of HGD results in a change of polarity of the residue (p.Ser189Ile). This variant is not found in GnomAD exomes (PM2) and has pathogenic predictions by numerous computational models (PP3). Uniprot reports this variant as associated with Alkaptonuria based on Beltrán-Valero de Bernabé et al. PMID 9529363 reporting 2 affected members of an Algerian family (PP5). Additionally, Rodriguez et al. PMID 11001939 demonstrated this variant to result in 3.4% residual enzyme activity and produce an insoluble protein in an E. coli model system. We interpret c.566G>T to be likely pathogenic.
Department Of Human Genetics, Institute Of Clinical And Translational Research, Biomedical Research Center, Slovak Academy Of Sciences RCV001376105 SCV004100982 pathogenic Alkaptonuria no assertion criteria provided research The variant was originally described in AKU patient in PMID:9529363. It has been submitted to the HGD gene mutation database (, DB-ID: AKU_00062).

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