Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV001823523 | SCV002073022 | uncertain significance | 3-hydroxy-3-methylglutaryl-CoA synthase deficiency | criteria provided, single submitter | clinical testing | The missense variant p.H234R in HMGCS2 (NM_005518.4) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.H234R variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.H234R missense variant is predicted to be damaging by both SIFT and PolyPhen2. The histidine residue at codon 234 of HMGCS2 is conserved in all mammalian species. The nucleotide c.701 in HMGCS2 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. |