ClinVar Miner

Submissions for variant NM_016169.4(SUFU):c.436C>T (p.Arg146Ter)

gnomAD frequency: 0.00001  dbSNP: rs1060501109
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000460887 SCV000544976 pathogenic Gorlin syndrome; Medulloblastoma 2023-10-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg146*) in the SUFU gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SUFU are known to be pathogenic (PMID: 22508808, 25403219, 33024317). This variant is present in population databases (no rsID available, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with medulloblastoma (PMID: 29753700). ClinVar contains an entry for this variant (Variation ID: 406388). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000519054 SCV000618320 pathogenic not provided 2022-08-29 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Published functional studies of a deletion resulting in the same protein effect (R146*) demonstrate a damaging effect: unable to repress transcriptional activation and no Gli3 expression when studied in the homozygous state (Makino et al., 2015); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25760946, 24686850, 25151357, 29706825, 31589614, 29753700)
Ambry Genetics RCV002329034 SCV002627613 pathogenic Hereditary cancer-predisposing syndrome 2024-04-15 criteria provided, single submitter clinical testing The p.R146* pathogenic mutation (also known as c.436C>T), located in coding exon 3 of the SUFU gene, results from a C to T substitution at nucleotide position 436. This changes the amino acid from an arginine to a stop codon within coding exon 3. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Revvity Omics, Revvity RCV000519054 SCV004238375 pathogenic not provided 2023-02-10 criteria provided, single submitter clinical testing

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