Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003041302 | SCV003441886 | uncertain significance | 3-hydroxy-3-methylglutaryl-CoA synthase deficiency | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 371 of the HMGCS2 protein (p.Ser371Cys). 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 HMGCS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2138012). 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 HMGCS2 protein function with a negative 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. |
| Ambry Genetics | RCV003041303 | SCV003687078 | uncertain significance | Inborn genetic diseases | 2021-04-01 | criteria provided, single submitter | clinical testing | The c.1112C>G (p.S371C) alteration is located in exon 6 (coding exon 6) of the HMGCS2 gene. This alteration results from a C to G substitution at nucleotide position 1112, causing the serine (S) at amino acid position 371 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |