ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.4254T>G (p.His1418Gln)

gnomAD frequency: 0.00015  dbSNP: rs201349007
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000768132 SCV000899083 uncertain significance Cohen syndrome 2021-03-30 criteria provided, single submitter clinical testing VPS13B NM_017890 exon 29 p.His1443Gln (c.4329T>G): This variant has not been reported in the literature but is present in 2/33552 Latino alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs201349007). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV000768132 SCV000955169 uncertain significance Cohen syndrome 2022-08-19 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1443 of the VPS13B protein (p.His1443Gln). This variant is present in population databases (rs201349007, gnomAD 0.006%). 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: 626047). 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: "Probably Damaging"; 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 RCV002332546 SCV002633268 uncertain significance Inborn genetic diseases 2023-12-28 criteria provided, single submitter clinical testing The c.4329T>G (p.H1443Q) alteration is located in exon 29 (coding exon 28) of the VPS13B gene. This alteration results from a T to G substitution at nucleotide position 4329, causing the histidine (H) at amino acid position 1443 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV000768132 SCV001456267 uncertain significance Cohen syndrome 2020-04-16 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV003396333 SCV004104485 uncertain significance VPS13B-related disorder 2024-09-27 no assertion criteria provided clinical testing The VPS13B c.4254T>G variant is predicted to result in the amino acid substitution p.His1418Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0058% 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.

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