Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000622697 | SCV000741269 | uncertain significance | Inborn genetic diseases | 2021-10-29 | criteria provided, single submitter | clinical testing | The c.5401G>T (p.V1801F) alteration is located in exon 34 (coding exon 33) of the VPS13B gene. This alteration results from a G to T substitution at nucleotide position 5401, causing the valine (V) at amino acid position 1801 to be replaced by a phenylalanine (F). The heterozygous missense change is ultra rare in healthy individuals:_x000D_ Based on data from the NHLBI Exome Sequencing Project (ESP), the VPS13B c.5401G>T alteration was not observed among 6,503 individuals tested. The alteration was observed in 10 out of 121,130 total alleles studied in ExAC (0.008%), with an allele frequency of 0.05% in the South Asian population. Allele frequency data for this nucleotide position are not currently available from the 1000 Genomes Project. This alteration is listed in the Database of Single Nucleotide Polymorphisms (dbSNP) rs547179338. Rare missense alleles commonly exhibit a deleterious effect on protein function (Kryukov, 2007; Tennessen, 2012; please note that some variants may appear to be rare due to ethnic underrepresentation in the database). _x000D_ IF USED, PULL THESE INTO REFERENCES:_x000D_ Kryukov GV, et al. (2007) Am J Hum Genet 80:727-739. Tennessen JA, et al. (2012) Science 337(64):64-69. The altered amino acid is conserved throughout evolution:_x000D_ The p.V1801 amino acid is highly conserved in available vertebrate species. In silico prediction is conflicting:_x000D_ The p.V1801F alteration is predicted to be possibly damaging by Polyphen and tolerated by SIFT in silico analyses. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Genome- |
RCV001578971 | SCV001806343 | uncertain significance | Cohen syndrome | 2021-07-22 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001578971 | SCV002188948 | uncertain significance | Cohen syndrome | 2022-10-31 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1801 of the VPS13B protein (p.Val1801Phe). This variant is present in population databases (rs547179338, gnomAD 0.05%). 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: 520921). 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 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. |
Natera, |
RCV001578971 | SCV002082578 | uncertain significance | Cohen syndrome | 2019-11-11 | no assertion criteria provided | clinical testing |