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

dbSNP: rs2107510544

Total submissions: 2

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 (http://hgddatabase.cvtisr.sk/, DB-ID: AKU_00062).