ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.10643C>T (p.Thr3548Ile)

gnomAD frequency: 0.00003  dbSNP: rs750693109
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002315388 SCV000849238 uncertain significance Inborn genetic diseases 2017-03-15 criteria provided, single submitter clinical testing The p.T3573I variant (also known as c.10718C>T), located in coding exon 55 of the VPS13B gene, results from a C to T substitution at nucleotide position 10718. The threonine at codon 3573 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001064675 SCV001229588 uncertain significance Cohen syndrome 2022-09-06 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 3573 of the VPS13B protein (p.Thr3573Ile). This variant is present in population databases (rs750693109, 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: 588894). 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.
Natera, Inc. RCV001064675 SCV002082751 uncertain significance Cohen syndrome 2020-02-11 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004742591 SCV005346895 uncertain significance VPS13B-related disorder 2024-06-12 no assertion criteria provided clinical testing The VPS13B c.10643C>T variant is predicted to result in the amino acid substitution p.Thr3548Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.085% of alleles in individuals of East Asian descent in gnomAD. Although we suspect that this variant may be benign, the clinical significance of this variant is classified as uncertain at this time due to insufficient functional and genetic evidence.

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