Submissions for variant NM_000187.4(HGD):c.125A>C (p.Glu42Ala)

gnomAD frequency: 0.00007  dbSNP: rs373921680

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001384280	SCV001583721	pathogenic	Alkaptonuria	2023-06-25	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as 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: 1071746). This missense change has been observed in individuals with alkaptonuria (PMID: 9529363, 25681086). This variant is present in population databases (rs373921680, gnomAD 0.009%). This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 42 of the HGD protein (p.Glu42Ala).
Fulgent Genetics, Fulgent Genetics	RCV001384280	SCV002792806	likely pathogenic	Alkaptonuria	2022-03-15	criteria provided, single submitter	clinical testing
Department Of Human Genetics, Institute Of Clinical And Translational Research, Biomedical Research Center, Slovak Academy Of Sciences	RCV001384280	SCV004098948	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_00008).