Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001981696 | SCV002221441 | uncertain significance | Cohen syndrome | 2022-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with leucine at codon 3524 of the VPS13B protein (p.Phe3524Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is present in population databases (rs781420614, gnomAD 0.09%). 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: 1444172). 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: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). 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 | RCV002562884 | SCV003683112 | uncertain significance | Inborn genetic diseases | 2022-09-08 | criteria provided, single submitter | clinical testing | The c.10572T>G (p.F3524L) alteration is located in exon 56 (coding exon 55) of the VPS13B gene. This alteration results from a T to G substitution at nucleotide position 10572, causing the phenylalanine (F) at amino acid position 3524 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Prevention |
RCV003923384 | SCV004740738 | uncertain significance | VPS13B-related disorder | 2024-02-12 | no assertion criteria provided | clinical testing | The VPS13B c.10497T>G variant is predicted to result in the amino acid substitution p.Phe3499Leu. This variant can also be described as c.10572T>G (p.Phe3524Leu) using an alternate transcript (NM_017890). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.087% of alleles in individuals of Latino descent in gnomAD, which is likely too common for an undocumented disease-causing variant. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |