ClinVar Miner

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

dbSNP: rs369517993
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Total submissions: 2
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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 (, DB-ID: AKU_00010).

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