Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV003476435 | SCV004199905 | likely pathogenic | Deficiency of hydroxymethylglutaryl-CoA lyase | 2022-06-17 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003476435 | SCV004389454 | pathogenic | Deficiency of hydroxymethylglutaryl-CoA lyase | 2023-06-27 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly289Alafs*6) in the HMGCL gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 37 amino acid(s) of the HMGCL protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with HMGCL-related conditions. This variant disrupts a region of the HMGCL protein in which other variant(s) (p.Phe305Tyrfs*10) have been determined to be pathogenic (PMID: 2443756, 6085636, 9463337). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |