ClinVar Miner

Submissions for variant NM_001352514.2(HLCS):c.1910C>T (p.Pro637Leu)

gnomAD frequency: 0.00005  dbSNP: rs536067980
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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 RCV001247264 SCV001420674 uncertain significance Holocarboxylase synthetase deficiency 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 490 of the HLCS protein (p.Pro490Leu). This variant is present in population databases (rs536067980, gnomAD 0.03%). 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: 971476). 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. 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. RCV001247264 SCV002083731 uncertain significance Holocarboxylase synthetase deficiency 2020-02-26 no assertion criteria provided clinical testing

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