Submissions for variant NM_152564.5(VPS13B):c.10514G>T (p.Arg3505Leu)

dbSNP: rs770999005

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001952448	SCV002198669	uncertain significance	Cohen syndrome	2022-07-18	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with leucine at codon 3530 of the VPS13B protein (p.Arg3530Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is present in population databases (rs770999005, gnomAD 0.02%). 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: 1430463). 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.
New York Genome Center	RCV001952448	SCV003925318	uncertain significance	Cohen syndrome	2022-04-06	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004041952	SCV004978117	uncertain significance	Inborn genetic diseases	2024-01-16	criteria provided, single submitter	clinical testing	The c.10589G>T (p.R3530L) alteration is located in exon 56 (coding exon 55) of the VPS13B gene. This alteration results from a G to T substitution at nucleotide position 10589, causing the arginine (R) at amino acid position 3530 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx	RCV005054389	SCV005687850	uncertain significance	not provided	2024-08-02	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences	RCV004743665	SCV005344663	uncertain significance	VPS13B-related disorder	2024-05-31	no assertion criteria provided	clinical testing	The VPS13B c.10514G>T variant is predicted to result in the amino acid substitution p.Arg3505Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.020% 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.