ClinVar Miner

Submissions for variant NM_016169.4(SUFU):c.368G>A (p.Arg123His)

gnomAD frequency: 0.00001  dbSNP: rs745958724
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001062420 SCV001227218 uncertain significance Gorlin syndrome; Medulloblastoma 2023-10-18 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 123 of the SUFU protein (p.Arg123His). This variant is present in population databases (rs745958724, gnomAD 0.003%). 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: 856862). 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 expected to disrupt SUFU 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.
Ambry Genetics RCV002348450 SCV002622095 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-06 criteria provided, single submitter clinical testing The p.R123H variant (also known as c.368G>A), located in coding exon 3 of the SUFU gene, results from a G to A substitution at nucleotide position 368. The arginine at codon 123 is replaced by histidine, an amino acid with highly 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.
GeneDx RCV003328649 SCV004035746 uncertain significance not provided 2023-03-13 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 24311597)

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