ClinVar Miner

Submissions for variant NM_001037811.2(HSD17B10):c.388C>T (p.Arg130Cys) (rs28935475)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics,Klinikum rechts der Isar RCV000012195 SCV000680262 pathogenic HSD10 disease 2017-10-25 criteria provided, single submitter clinical testing
Victorian Clinical Genetics Services,Murdoch Childrens Research Institute RCV000012195 SCV001244963 pathogenic HSD10 disease 2018-02-24 criteria provided, single submitter clinical testing A hemizygous missense variant, NM_001037811.2(HSD17B10):c.388C>T, has been identified in exon 4 of 6 of the HSD17B10 gene. The variant is predicted to result in a major amino acid change from arginine to cysteine at position 130 of the protein (NP_004484.1(HSD17B10):p.(Arg130Cys)). The arginine at this position has high conservation (100 vertebrates, UCSC), and is located within the short chain dehydrogenase functional domain. In-silico predictions for this variant are consistently pathogenic (Polyphen, SIFT, CADD, Mutation Taster). The variant is absent in population databases (gnomAD, dbSNP, 1000G). The variant has been previously described as pathogenic and has previously been reported as de-novo or maternally inherited in multiple families with HSD10 mitochondrial disease (ClinVar, OMIM, Zschocke J. (2012)). Additionally, immunoanalysis and studies of enzyme activity showed decreased amount of the enzyme and complete absence of enzyme activity (Yang S.Y., et al. (2009)). Analysis of parental samples indicated this variant to be maternally inherited. Based on the information available at the time of curation, this variant has been classified as PATHOGENIC.
Invitae RCV001224055 SCV001396232 pathogenic not provided 2019-06-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 130 of the HSD17B10 protein (p.Arg130Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency (PMID: 12696021, 18996107, 23266819). ClinVar contains an entry for this variant (Variation ID: 11442). This variant has been reported to affect HSD17B10 protein function (PMID: 12696021, 24549042). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000012195 SCV000032429 pathogenic HSD10 disease 2010-02-01 no assertion criteria provided literature only

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