ClinVar Miner

Submissions for variant NM_016169.4(SUFU):c.256G>A (p.Glu86Lys)

gnomAD frequency: 0.00001  dbSNP: rs770989077
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001015983 SCV001176884 uncertain significance Hereditary cancer-predisposing syndrome 2024-10-17 criteria provided, single submitter clinical testing The p.E86K variant (also known as c.256G>A), located in coding exon 2 of the SUFU gene, results from a G to A substitution at nucleotide position 256. The glutamic acid at codon 86 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious 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 RCV001047839 SCV001211821 uncertain significance Gorlin syndrome; Medulloblastoma 2025-01-23 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 86 of the SUFU protein (p.Glu86Lys). This variant is present in population databases (rs770989077, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with SUFU-related conditions. ClinVar contains an entry for this variant (Variation ID: 821503). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SUFU protein function with a negative predictive value of 80%. 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.
Fulgent Genetics, Fulgent Genetics RCV002479213 SCV002787572 uncertain significance Gorlin syndrome; Medulloblastoma; Familial meningioma; Joubert syndrome 32 2022-02-17 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004553556 SCV004118275 uncertain significance SUFU-related disorder 2022-11-16 criteria provided, single submitter clinical testing The SUFU c.256G>A variant is predicted to result in the amino acid substitution p.Glu86Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00090% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-104268999-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Baylor Genetics RCV003461354 SCV004205672 uncertain significance Familial meningioma 2023-09-28 criteria provided, single submitter clinical testing
GeneDx RCV004761873 SCV005372435 uncertain significance not provided 2023-06-20 criteria provided, single submitter clinical testing Not observed at 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
Quest Diagnostics Nichols Institute San Juan Capistrano RCV004761873 SCV005626200 uncertain significance not provided 2024-05-14 criteria provided, single submitter clinical testing The SUFU c.256G>A (p.Glu86Lys) variant has not been reported in individuals with SUFU-related conditions in the published literature. The frequency of this variant in the general population, 0.000004 (1/249052 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is deleterious or benign. Based on the available information, we are unable to determine the clinical significance of this variant.

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