Submissions for variant NM_152564.5(VPS13B):c.6230G>A (p.Arg2077His)

dbSNP: rs747116389

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001240940	SCV001413925	uncertain significance	Cohen syndrome	2022-08-22	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 2102 of the VPS13B protein (p.Arg2102His). This variant is present in population databases (rs747116389, gnomAD 0.005%). 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: 966292). 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 histidine 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.
GeneDx	RCV002469360	SCV002765221	uncertain significance	not provided	2022-12-12	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV003246796	SCV003938456	uncertain significance	Inborn genetic diseases	2023-06-13	criteria provided, single submitter	clinical testing	The c.6305G>A (p.R2102H) alteration is located in exon 36 (coding exon 35) of the VPS13B gene. This alteration results from a G to A substitution at nucleotide position 6305, causing the arginine (R) at amino acid position 2102 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc.	RCV001240940	SCV002082604	uncertain significance	Cohen syndrome	2020-06-25	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004743355	SCV005358851	uncertain significance	VPS13B-related disorder	2024-05-23	no assertion criteria provided	clinical testing	The VPS13B c.6230G>A variant is predicted to result in the amino acid substitution p.Arg2077His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0047% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.