Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001928415 | SCV002180227 | pathogenic | Holocarboxylase synthetase deficiency | 2023-02-16 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the HLCS protein in which other variant(s) (p.Arg665*) have been determined to be pathogenic (PMID: 10190325, 16134170, 27114915). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 1413934). This variant has not been reported in the literature in individuals affected with HLCS-related conditions. This variant is present in population databases (rs760372711, gnomAD 0.003%). This sequence change results in a frameshift in the HLCS gene (p.Val641Cysfs*108). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 86 amino acid(s) of the HLCS protein and extend the protein by 21 additional amino acid residues. |