ClinVar Miner

Submissions for variant NM_016169.4(SUFU):c.1157G>A (p.Arg386Lys)

gnomAD frequency: 0.00001  dbSNP: rs767814106
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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 RCV000819970 SCV000960659 uncertain significance Gorlin syndrome; Medulloblastoma 2024-05-28 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 386 of the SUFU protein (p.Arg386Lys). This variant also falls at the last nucleotide of exon 9, which is part of the consensus splice site for this exon. This variant is present in population databases (rs767814106, gnomAD 0.006%). 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: 662350). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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 RCV004029023 SCV005026339 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-17 criteria provided, single submitter clinical testing The p.R386K variant (also known as c.1157G>A), located in coding exon 9 of the SUFU gene, results from a G to A substitution at nucleotide position 1157. The amino acid change results in arginine to lysine at codon 386, an amino acid with highly similar properties. However, this change occurs in the last base pair of coding exon 9, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. This amino acid position is highly conserved in available vertebrate species. In addition, as a missense substitution this 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.
Fulgent Genetics, Fulgent Genetics RCV005029509 SCV005660578 uncertain significance Medulloblastoma; Familial meningioma; Joubert syndrome 32; Basal cell nevus syndrome 2 2024-03-06 criteria provided, single submitter clinical testing

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