Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002817832 | SCV003602590 | uncertain significance | Inborn genetic diseases | 2022-02-02 | criteria provided, single submitter | clinical testing | The c.752C>G (p.T251S) alteration is located in exon 9 (coding exon 9) of the DCLRE1C gene. This alteration results from a C to G substitution at nucleotide position 752, causing the threonine (T) at amino acid position 251 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003611625 | SCV004531405 | uncertain significance | Severe combined immunodeficiency due to DCLRE1C deficiency | 2023-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 251 of the DCLRE1C protein (p.Thr251Ser). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with DCLRE1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 2275234). 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 DCLRE1C 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. |