Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001242571 | SCV001415666 | uncertain significance | Cohen syndrome | 2024-09-27 | 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 1111 of the VPS13B protein (p.Pro1111Leu). This variant is present in population databases (rs576973103, gnomAD 0.08%). 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: 967612). 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 VPS13B 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. |
Ambry Genetics | RCV002322152 | SCV002606591 | uncertain significance | Inborn genetic diseases | 2018-01-31 | criteria provided, single submitter | clinical testing | The p.P1111L variant (also known as c.3332C>T), located in coding exon 22 of the VPS13B gene, results from a C to T substitution at nucleotide position 3332. The proline at codon 1111 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001242571 | SCV002079556 | uncertain significance | Cohen syndrome | 2020-02-21 | no assertion criteria provided | clinical testing |