ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.1087G>A (p.Glu363Lys)

gnomAD frequency: 0.00001  dbSNP: rs116951775
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001238925 SCV001411761 uncertain significance Cohen syndrome 2022-10-24 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 363 of the VPS13B protein (p.Glu363Lys). This variant is present in population databases (rs116951775, 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: 964660). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt VPS13B 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.
Genome-Nilou Lab RCV001238925 SCV001806192 uncertain significance Cohen syndrome 2021-07-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV002430021 SCV002726246 uncertain significance Inborn genetic diseases 2018-12-03 criteria provided, single submitter clinical testing The p.E363K variant (also known as c.1087G>A), located in coding exon 7 of the VPS13B gene, results from a G to A substitution at nucleotide position 1087. The glutamic acid at codon 363 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001238925 SCV002079458 uncertain significance Cohen syndrome 2020-11-19 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV003918794 SCV004732712 uncertain significance VPS13B-related disorder 2024-08-06 no assertion criteria provided clinical testing The VPS13B c.1087G>A variant is predicted to result in the amino acid substitution p.Glu363Lys. This variant was reported in the compound heterozygous state in an individual with short stature, global developmental delay, and attention-deficit/hyperactivity disorder; however, this individual was not considered to be affected by Cohen syndrome (Patient #42 in Table 3 and Table S2, Gippert et al. 2023. PubMed ID: 37940764). This variant is reported in 0.020% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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