Submissions for variant NM_001042492.3(NF1):c.6006G>C (p.Gln2002His)

dbSNP: rs1555534432

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000576617	SCV000678219	uncertain significance	Neurofibromatosis, type 1	2017-08-01	criteria provided, single submitter	clinical testing	NF1 NM_001042492.2 exon40 p.Gln2002His (c.6006G>C): This variant has not been reported in the literature and is not present in large control databases. Evolutionary conservation and computational predictive tools for this variant are unclear. Of note, a different variant resulting in the same amino acid change at this position has been reported in 1 individual with a clinical suspicion of NF1 (reported as c.5943G>C, p.Gln1981His, Bianchessi 2015 PMID:26740943). In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000576617	SCV001493392	pathogenic	Neurofibromatosis, type 1	2024-04-22	criteria provided, single submitter	clinical testing	This sequence change affects codon 1981 of the NF1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NF1 protein. This variant also falls at the last nucleotide of exon 39, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with neurofibromatosis type 1 (Invitae). ClinVar contains an entry for this variant (Variation ID: 487463). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab	RCV000576617	SCV002560927	uncertain significance	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV004796237	SCV005417009	uncertain significance	Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis		criteria provided, single submitter	clinical testing	PM2_Supporting+PP3+PS4_Supporting+PP4