Submissions for variant NM_000187.4(HGD):c.158G>A (p.Arg53Gln)

gnomAD frequency: 0.00006  dbSNP: rs200808744

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000412076	SCV000486375	likely pathogenic	Alkaptonuria	2016-05-24	criteria provided, single submitter	clinical testing
Invitae	RCV000412076	SCV000942825	pathogenic	Alkaptonuria	2023-12-26	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 53 of the HGD protein (p.Arg53Gln). This variant is present in population databases (rs200808744, gnomAD 0.01%). This missense change has been observed in individual(s) with alkaptonuria (PMID: 25681086, 25804398; Invitae). ClinVar contains an entry for this variant (Variation ID: 370939). 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 HGD protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV001726153	SCV001962514	likely pathogenic	not provided	2021-07-01	criteria provided, single submitter	clinical testing
Department Of Human Genetics, Institute Of Clinical And Translational Research, Biomedical Research Center, Slovak Academy Of Sciences	RCV000412076	SCV004098926	pathogenic	Alkaptonuria		no assertion criteria provided	research	The variant was originally described in AKU patients in PMID:25804398 and PMID: 25681086. It has been submitted to the HGD gene mutation database (http://hgddatabase.cvtisr.sk/, DB-ID: AKU_00AKU_00152).