Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001277486 | SCV002270358 | uncertain significance | Holocarboxylase synthetase deficiency | 2023-12-18 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 415 of the HLCS protein (p.Ser415Tyr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 989619). 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 with a positive predictive value of 80%. 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, |
RCV001277486 | SCV001464441 | uncertain significance | Holocarboxylase synthetase deficiency | 2020-08-13 | no assertion criteria provided | clinical testing |