Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001203383 | SCV001374546 | uncertain significance | Cohen syndrome | 2019-10-15 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with threonine at codon 2967 of the VPS13B protein (p.Met2967Thr). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with VPS13B-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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 | RCV003373024 | SCV004092976 | uncertain significance | Inborn genetic diseases | 2023-08-21 | criteria provided, single submitter | clinical testing | The c.8900T>C (p.M2967T) alteration is located in exon 49 (coding exon 48) of the VPS13B gene. This alteration results from a T to C substitution at nucleotide position 8900, causing the methionine (M) at amino acid position 2967 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Prevention |
RCV003398926 | SCV004121156 | uncertain significance | VPS13B-related disorder | 2022-10-18 | criteria provided, single submitter | clinical testing | The VPS13B c.8825T>C variant is predicted to result in the amino acid substitution p.Met2942Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0016% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-100832181-T-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Natera, |
RCV001203383 | SCV002082690 | uncertain significance | Cohen syndrome | 2020-03-10 | no assertion criteria provided | clinical testing |