Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002307362 | SCV002600634 | uncertain significance | not specified | 2024-02-01 | criteria provided, single submitter | clinical testing | Variant summary: HSD17B10 c.364C>G (p.Leu122Val) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 5e-06 in 1209658 control chromosomes in the gnomAD database, including 3 hemizygotes. c.364C>G has been reported in the literature in a male patient affected with 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency (Ofman_2003, Poll-The_2004). In addition, the variant has also been reported in ten individuals from four unrelated French-Canadian families: two asymptomatic male individuals, four asymptomatic female individuals and one female with mild intellectual deficiency and speech difficulty, one male affected with spastic paraplegia and dysarthria who had a reportedly pathogenic de novo variant in SPAST which could account for his phenotype, one male with dystonic episodes which gradually diminished without treatment, and one female affected with developmental delay and axial hypotonia who had a co-occurring pathogenic variant in CACNA1A resulting in a diagnosis of episodic ataxia (Waters_2019). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function and found the variant did not affect protein expression, but resulted in 2-3 % of normal MHBD activity in vitro (Ofman_2003). The following publications have been ascertained in the context of this evaluation (PMID: 12696021, 16148061, 15059617, 31654490). ClinVar contains an entry for this variant (Variation ID: 11443). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| OMIM | RCV000012196 | SCV000032430 | pathogenic | HSD10 mitochondrial disease | 2003-05-01 | no assertion criteria provided | literature only |