Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001248081 | SCV001421546 | uncertain significance | Cohen syndrome | 2022-09-06 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 2124 of the VPS13B protein (p.Met2124Ile). This variant is not present in population databases (gnomAD no frequency). 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: 972122). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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 | RCV002570367 | SCV003635600 | uncertain significance | Inborn genetic diseases | 2022-07-20 | criteria provided, single submitter | clinical testing | The c.6372G>T (p.M2124I) alteration is located in exon 36 (coding exon 35) of the VPS13B gene. This alteration results from a G to T substitution at nucleotide position 6372, causing the methionine (M) at amino acid position 2124 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Natera, |
RCV001248081 | SCV002082607 | uncertain significance | Cohen syndrome | 2020-09-03 | no assertion criteria provided | clinical testing | |
| Prevention |
RCV004743365 | SCV005361466 | uncertain significance | VPS13B-related disorder | 2024-09-03 | no assertion criteria provided | clinical testing | The VPS13B c.6297G>T variant is predicted to result in the amino acid substitution p.Met2099Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |