Submissions for variant NM_001042492.3(NF1):c.7701dup (p.Lys2568fs)

dbSNP: rs1060500295

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000660119	SCV000782109	pathogenic	Neurofibromatosis, type 1	2016-11-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002424563	SCV001189078	pathogenic	Hereditary cancer-predisposing syndrome; Cardiovascular phenotype	2018-06-04	criteria provided, single submitter	clinical testing	The c.7638dupC pathogenic mutation, located in coding exon 51 of the NF1 gene, results from a duplication of C at nucleotide position 7638, causing a translational frameshift with a predicted alternate stop codon (p.K2547Qfs*9). 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.
Invitae	RCV000660119	SCV001373973	pathogenic	Neurofibromatosis, type 1	2023-06-07	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 547695). This variant is also known as 7633insC. This premature translational stop signal has been observed in individual(s) with neurofibromatosis type 1 (PMID: 10712197). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys2547Glnfs*9) 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).
Genome-Nilou Lab	RCV000660119	SCV002560584	pathogenic	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
GeneDx	RCV002289949	SCV002578647	pathogenic	not provided	2022-10-27	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); 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; This variant is associated with the following publications: (PMID: 10712197)
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000660119	SCV004805351	uncertain significance	Neurofibromatosis, type 1	2024-03-25	criteria provided, single submitter	research