Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002647318 | SCV003514020 | pathogenic | 3-hydroxy-3-methylglutaryl-CoA synthase deficiency | 2023-12-06 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr242*) in the HMGCS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HMGCS2 are known to be pathogenic (PMID: 20346956, 23751782, 25511235). This variant is present in population databases (rs145838142, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with HMGCS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2194069). For these reasons, this variant has been classified as Pathogenic. |
| Johns Hopkins Genomics, |
RCV002647318 | SCV003839120 | likely pathogenic | 3-hydroxy-3-methylglutaryl-CoA synthase deficiency | 2022-12-07 | criteria provided, single submitter | clinical testing | This HMGCS2 variant (rs145838142) is rare (<0.1%) in a large population dataset (gnomAD: 16/282718 total alleles; 0.006%; no homozygotes) and has not been reported in ClinVar or the literature, to our knowledge. This stopgain variant in exon 4 results in a premature termination codon (PTC) likely leading to nonsense-mediated decay and lack of protein production. We consider c.726C>G (p.Tyr242Ter) to be likely pathogenic. |