Submissions for variant NM_004493.3(HSD17B10):c.634A>G (p.Lys212Glu)

dbSNP: rs886041974

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000365072	SCV000330790	pathogenic	not provided	2016-09-15	criteria provided, single submitter	clinical testing	Introduction of the K212E variant into E. coli found that it is associated with significantly reduceddehydrogenase activity of the SDR5C1 enzyme compared to wild-type (Falk et al., 2016).Additional functional analysis found that the K212E variant also results in impaired 5' processingand methylation of mt-tRNAs (Falk et al., 2016). The K212E variant is located with the substratespecificity loop and is predicted to alter active site closure of the SDR5C1 enzyme (Falk et al.,2016). The K212E variant was not observed in approximately 6,500 individuals of European andAfrican American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a commonbenign variant in these populations. The K212E variant is a non-conservative amino acidsubstitution, which is likely to impact secondary protein structure as these residues differ inpolarity, charge, size and/or other properties. This substitution occurs at a position that isconserved across species. In silico analysis is inconsistent in its predictions as to whether or notthe variant is damaging to the protein structure/function. In summary, we interpret K212E to be apathogenic variant.
CeGaT Center for Human Genetics Tuebingen	RCV000365072	SCV002822030	likely pathogenic	not provided	2022-12-01	criteria provided, single submitter	clinical testing	HSD17B10: PM1, PM2, PS3:Moderate, PS4:Supporting
OMIM	RCV000488602	SCV000575904	pathogenic	HSD10 mitochondrial disease	2017-05-10	no assertion criteria provided	literature only