ClinVar Miner

Submissions for variant NM_001352514.2(HLCS):c.1151T>G (p.Leu384Arg)

dbSNP: rs119103227
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000815726 SCV000956194 likely pathogenic Holocarboxylase synthetase deficiency 2022-04-28 criteria provided, single submitter clinical testing Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt HLCS protein function. This variant disrupts the p.Leu237 amino acid residue in HLCS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7842009, 8541348). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 658832). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 237 of the HLCS protein (p.Leu237Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with HLCS-related conditions.

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