Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001365368 | SCV001561636 | uncertain significance | Cohen syndrome | 2022-03-26 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 630 of the VPS13B protein (p.Ala630Thr). This variant is present in population databases (rs768721417, gnomAD 0.01%). 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: 1056522). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 | RCV002550053 | SCV003657357 | uncertain significance | Inborn genetic diseases | 2022-11-17 | criteria provided, single submitter | clinical testing | The c.1888G>A (p.A630T) alteration is located in exon 14 (coding exon 13) of the VPS13B gene. This alteration results from a G to A substitution at nucleotide position 1888, causing the alanine (A) at amino acid position 630 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
New York Genome Center | RCV001365368 | SCV004046620 | uncertain significance | Cohen syndrome | 2022-11-29 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001365368 | SCV002079491 | uncertain significance | Cohen syndrome | 2020-02-07 | no assertion criteria provided | clinical testing |