Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001923989 | SCV002199364 | pathogenic | Deficiency of hydroxymethylglutaryl-CoA lyase | 2022-04-08 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp204Thrfs*11) in the HMGCL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HMGCL are known to be pathogenic (PMID: 9817922, 17692550, 23465862). 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. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV001923989 | SCV004199881 | likely pathogenic | Deficiency of hydroxymethylglutaryl-CoA lyase | 2024-02-06 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV001923989 | SCV005398972 | pathogenic | Deficiency of hydroxymethylglutaryl-CoA lyase | 2024-10-10 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.5, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with HMG-CoA lyase deficiency (MIM#246450). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (v2, v3 and v4). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Pathogenic NMD-predicted variants have been reported in multiple unrelated individuals with HMG-CoA lyase deficiency (DECIPHER, PMID: 33996180). (SP) 0803 - This variant has limited previous evidence of pathogenicity in unrelated individuals. This variant has been classified as likely pathogenic and pathogenic by clinical laboratories in ClinVar. (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) |