Submissions for variant NM_001042492.3(NF1):c.2033del (p.Pro678fs)

dbSNP: rs587781807

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000492337	SCV000581312	pathogenic	Hereditary cancer-predisposing syndrome	2015-10-23	criteria provided, single submitter	clinical testing	Thec.2033delCpathogenic mutation, located in codingexon18 of theNF1gene, results from a deletion of one nucleotide at position 2033, causing a translationalframeshiftwith a predicted alternate stopcodon. This alteration has previously been identified in individuals with clinical features consistent with neurofibromatosis type 1 (NF1) (Fashold et al. Am. J. Hum. Genet. 2000; 66(3):790-818; Wimmer et al.Hum. Mutat. 2007; 28(6):599-612; Pasmant et al. Eur. J. Hum. Genet. 2014; 23(5):596-601 ).In addition to the clinical data presented in the literature, since premature stop codons are typically deleterious in nature, this alterationis interpreted as a disease-causing mutation (ACMGRecommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000558816	SCV000628406	pathogenic	Neurofibromatosis, type 1	2023-12-21	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Pro678Argfs*10) in the NF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with neurofibromatosis type 1 (PMID: 17311297, 21520333; Invitae). ClinVar contains an entry for this variant (Variation ID: 428991). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV001556086	SCV001777603	pathogenic	not provided	2022-07-25	criteria provided, single submitter	clinical testing	Frameshift 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; Not observed at significant frequency in large population cohorts (gnomAD); Observed in an individual with breast cancer (Palmer et al., 2020); This variant is associated with the following publications: (PMID: 25074460, 14722917, 10712197, 17311297, 22155606, 12522551, 30612635, 32427313)
Genome-Nilou Lab	RCV000558816	SCV002561726	pathogenic	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003464061	SCV004198396	pathogenic	Juvenile myelomonocytic leukemia	2023-07-26	criteria provided, single submitter	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001556086	SCV001979528	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001556086	SCV001979955	pathogenic	not provided		no assertion criteria provided	clinical testing