Submissions for variant NM_016169.4(SUFU):c.71del (p.Pro24fs)

dbSNP: rs587776579

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001385138	SCV001584895	pathogenic	Gorlin syndrome; Medulloblastoma	2023-06-30	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Pro24Argfs*72) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with medulloblastoma (PMID: 19833601, 29186568, 29753700). ClinVar contains an entry for this variant (Variation ID: 3573). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV003298027	SCV004001033	pathogenic	Hereditary cancer-predisposing syndrome	2023-04-07	criteria provided, single submitter	clinical testing	The c.71delC variant, located in coding exon 1 of the SUFU gene, results from a deletion of one nucleotide at nucleotide position 71, causing a translational frameshift with a predicted alternate stop codon (p.P24Rfs*72). This alteration has been observed in at least one individual with a personal and/or family history that is consistent with SUFU-related disease (Ambry internal data). In addition, this alteration has been identified in multiple infants diagnosed with medulloblastoma (Brugières L et al. J Med Genet, 2010 Feb;47:142-4; Guerrini-Rousseau L et al. J Med Genet, 2022 Jun;59:1123-32), as well as in a male child with congenital ocularmotor apraxia (Serpieri V et al. J Med Genet, 2022 Sep;59:888-894). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, 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.
OMIM	RCV002291208	SCV000023920	pathogenic	Medulloblastoma	2010-02-01	no assertion criteria provided	literature only
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001573665	SCV001799882	pathogenic	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001573665	SCV001808422	pathogenic	not provided		no assertion criteria provided	clinical testing
OMIM	RCV003227597	SCV003925590	pathogenic	Basal cell nevus syndrome 2	2010-02-01	no assertion criteria provided	literature only