Submissions for variant NM_000187.4(HGD):c.1114G>A (p.Gly372Arg)

dbSNP: rs1940645842

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001067792	SCV001232872	likely pathogenic	Alkaptonuria	2023-03-10	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 861290). This missense change has been observed in individual(s) with alkaptonuria (PMID: 33621656; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 372 of the HGD protein (p.Gly372Arg).
Laboratory of Inherited Metabolic Diseases, Research centre for medical genetics	RCV001067792	SCV001364398	likely pathogenic	Alkaptonuria	2020-03-03	criteria provided, single submitter	clinical testing	Severe damage of the musculoskeletal system
Department Of Human Genetics, Institute Of Clinical And Translational Research, Biomedical Research Center, Slovak Academy Of Sciences	RCV001067792	SCV004100967	pathogenic	Alkaptonuria		no assertion criteria provided	research	The variant was originally described in AKU patient in PMID:34504318 and PMID:33621656. It has been submitted to the HGD gene mutation database (http://hgddatabase.cvtisr.sk/, DB-ID: AKU_00234).