Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001209247 | SCV001380672 | uncertain significance | Cohen syndrome | 2022-10-05 | 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 354 of the VPS13B protein (p.Pro354Leu). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. ClinVar contains an entry for this variant (Variation ID: 939797). 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 VPS13B 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. |
| Ambry Genetics | RCV004033765 | SCV004978118 | uncertain significance | Inborn genetic diseases | 2023-09-20 | criteria provided, single submitter | clinical testing | The c.1061C>T (p.P354L) alteration is located in exon 8 (coding exon 7) of the VPS13B gene. This alteration results from a C to T substitution at nucleotide position 1061, causing the proline (P) at amino acid position 354 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Natera, |
RCV001209247 | SCV002079456 | uncertain significance | Cohen syndrome | 2020-07-10 | no assertion criteria provided | clinical testing |