Submissions for variant NM_000187.4(HGD):c.1201G>C (p.Glu401Gln)

dbSNP: rs767159114

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000409498	SCV000487100	likely pathogenic	Alkaptonuria	2016-10-05	criteria provided, single submitter	clinical testing
Invitae	RCV000409498	SCV002231322	pathogenic	Alkaptonuria	2021-02-18	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with alkaptonuria (PMID: 14978662, 25804398, 19862842). ClinVar contains an entry for this variant (Variation ID: 371502). This variant is present in population databases (rs767159114, ExAC 0.001%). This sequence change replaces glutamic acid with glutamine at codon 401 of the HGD protein (p.Glu401Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine.
Department Of Human Genetics, Institute Of Clinical And Translational Research, Biomedical Research Center, Slovak Academy Of Sciences	RCV000409498	SCV004100976	pathogenic	Alkaptonuria		no assertion criteria provided	research	The variant was originally described in AKU patient in PMID:14978662. It has been submitted to the HGD gene mutation database (http://hgddatabase.cvtisr.sk/, DB-ID: AKU_00102).