ClinVar Miner

Submissions for variant NM_001352514.2(HLCS):c.1918A>G (p.Met640Val)

gnomAD frequency: 0.00001  dbSNP: rs772156741
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000799673 SCV000939348 uncertain significance Holocarboxylase synthetase deficiency 2022-07-11 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 493 of the HLCS protein (p.Met493Val). This variant is present in population databases (rs772156741, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with HLCS-related conditions. ClinVar contains an entry for this variant (Variation ID: 645566). 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 not expected to disrupt HLCS protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Natera, Inc. RCV000799673 SCV002083730 uncertain significance Holocarboxylase synthetase deficiency 2020-09-16 no assertion criteria provided clinical testing

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