Submissions for variant NM_000187.4(HGD):c.1120G>C (p.Asp374His)

dbSNP: rs981454067

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000664925	SCV000788959	uncertain significance	Alkaptonuria	2017-01-09	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000664925	SCV002793082	uncertain significance	Alkaptonuria	2022-05-16	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000664925	SCV003525344	pathogenic	Alkaptonuria	2021-11-24	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 550232). This missense change has been observed in individual(s) with alkaptonuria (PMID: 23430897, 25681086). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 374 of the HGD protein (p.Asp374His). 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. For these reasons, this variant has been classified as Pathogenic.
Department Of Human Genetics, Institute Of Clinical And Translational Research, Biomedical Research Center, Slovak Academy Of Sciences	RCV000664925	SCV004100942	pathogenic	Alkaptonuria		no assertion criteria provided	research	The variant was originally described in AKU patient in PMID:23430897. It has been submitted to the HGD gene mutation database (http://hgddatabase.cvtisr.sk/, DB-ID: AKU_00148).