ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.4331A>T (p.Lys1444Met)

dbSNP: rs199474781
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Medical Genomics Laboratory, Department of Genetics UAB RCV000856626 SCV000999187 pathogenic Neurofibromatosis, type 1 2019-06-05 criteria provided, single submitter clinical testing
Invitae RCV000856626 SCV001419883 uncertain significance Neurofibromatosis, type 1 2019-11-11 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Lys1423 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1568247, 11735023, 11857752, 23244495, 16786508, 27322474). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been reported to affect NF1 protein function (PMID: 1587809). This variant has been observed in individual(s) with clinical features of neurofibromatosis type 1 (PMID: 29618358). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with methionine at codon 1423 of the NF1 protein (p.Lys1423Met). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and methionine.

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