ClinVar Miner

Submissions for variant NM_001352514.2(HLCS):c.2527C>T (p.Gln843Ter)

gnomAD frequency: 0.00001  dbSNP: rs1466111134
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000669070 SCV000793771 likely pathogenic Holocarboxylase synthetase deficiency 2017-08-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000669070 SCV003003599 likely pathogenic Holocarboxylase synthetase deficiency 2022-03-09 criteria provided, single submitter clinical testing This variant disrupts a region of the HLCS protein in which other variant(s) (p.Pro709Leu) have been observed in individuals with HLCS-related conditions (PMID: 27604308). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Experimental studies have shown that this premature translational stop signal affects HLCS function (PMID: 11124959). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 553590). This variant is also known as a 31-amino acid deletion ending at Leu-695. This variant has not been reported in the literature in individuals affected with HLCS-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Gln696*) in the HLCS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 31 amino acid(s) of the HLCS protein. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Baylor Genetics RCV000669070 SCV005059682 likely pathogenic Holocarboxylase synthetase deficiency 2024-03-14 criteria provided, single submitter clinical testing

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