ClinVar Miner

Submissions for variant NM_016169.3(SUFU):c.1028G>A (p.Arg343His) (rs79299301)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000260834 SCV000360091 uncertain significance Medulloblastoma 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV000466509 SCV000544991 uncertain significance Gorlin syndrome; Medulloblastoma 2019-12-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 343 of the SUFU protein (p.Arg343His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs79299301, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with SUFU-related disease. ClinVar contains an entry for this variant (Variation ID: 135285). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant has uncertain impact on SUFU function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000566455 SCV000675276 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-17 criteria provided, single submitter clinical testing Insufficient evidence
Fulgent Genetics,Fulgent Genetics RCV000763641 SCV000894512 uncertain significance Gorlin syndrome; Medulloblastoma; Meningioma, familial; JOUBERT SYNDROME 32 2018-10-31 criteria provided, single submitter clinical testing
ITMI RCV000122100 SCV000086315 not provided not specified 2013-09-19 no assertion provided reference population

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