Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| New York Genome Center | RCV001291736 | SCV001480327 | likely pathogenic | HSD10 mitochondrial disease | 2019-09-17 | criteria provided, single submitter | clinical testing | The de novo c.164G>A (p.Gly55Glu) variant identified in the HSD17B10 gene substitutes a completely conserved Glycine for Glutamic acid at amino acid 55/262 (coding exon 2/6). This variant is absent from gnomAD and ExAC, suggesting it is not a common benign variant in the populations represented in these databases. In silico algorithms predict this variant to be Deleterious (Provean; score: -6.61) and Damaging (SIFT; score: 0.000) to the function of the canonical transcript. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. The p.Gly55 residue is not within a functional domain of HSD17B10, but is within a region of the protein between the NAD Binding and Subunit Interaction domains where another missense variant has been reported in affected individuals [PMID: 22132097; PMID: 27295195]. Given the presence of this variant as a de novo variant in the affected individual, its absence in population databases, and in silico predictions of a damaging effect on the function of the canonical transcript, the c.164G>A (p.Gly55Glu) variant identified in the HSD17B10 gene is reported here as Likely Pathogenic. |