Submissions for variant NM_000187.4(HGD):c.140C>T (p.Ser47Leu)

dbSNP: rs369517993

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV003387491	SCV004848739	likely pathogenic	Alkaptonuria	2022-08-26	criteria provided, single submitter	clinical testing	The p.Ser47Leu variant in HGD has been reported in 5 individuals with alkaptonuria either as homozygous or compound heterozygous with a pathogenic variant (Zatkova 2001 PMID: 11017803, Ascher 2019 PMID: 30737480), and was absent in large population databases. Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive alkaptonuria. ACMG/AMP criteria applied: PM3_Strong, PM2_Supporting, PP3.
Department Of Human Genetics, Institute Of Clinical And Translational Research, Biomedical Research Center, Slovak Academy Of Sciences	RCV003387491	SCV004098978	pathogenic	Alkaptonuria		no assertion criteria provided	research	The variant was described in AKU patients in PMID:23430897 and PMID:30737480. It has been submitted to the HGD gene mutation database (http://hgddatabase.cvtisr.sk/, DB-ID: AKU_00010).