Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002380514 | SCV002673536 | uncertain significance | Inborn genetic diseases | 2021-09-02 | criteria provided, single submitter | clinical testing | The p.R25C variant (also known as c.73C>T), located in coding exon 1 of the BSCL2 gene, results from a C to T substitution at nucleotide position 73. The arginine at codon 25 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003776384 | SCV004615444 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2024-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 25 of the BSCL2 protein (p.Arg25Cys). This variant is present in population databases (rs771754989, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of BSCL2-related conditions (internal data). ClinVar contains an entry for this variant (Variation ID: 1758718). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt BSCL2 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. |