ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.479G>A (p.Arg160Lys)

dbSNP: rs199474752
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002315795 SCV000663249 likely pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2017-07-26 criteria provided, single submitter clinical testing The c.479G>A variant (also known as p.R160K), located in coding exon 4 of the NF1 gene, results from a G to A substitution at nucleotide position 479. The amino acid change results in arginine to lysine at codon 160, an amino acid with highly similar properties. However, this change occurs in the last base pair of coding exon 4, which makes it likely to have some effect on normal mRNA splicing. This alteration was detected in one individual meeting clinical diagnostic criteria for neurofibromatosis type 1 (NF1) (Ambry internal data), as well as one individual from a prospective cohort of patients with clinical suspicion of NF1 (Pasmant E et al. Eur. J. Hum. Genet., 2015 May;23:596-601). A different nucleotide change at the same position (c.479G>C) has been identified in two individuals meeting NF1 clinical diagnostic criteria and was shown via mRNA analysis to result in exon-skipping (Wimmer K et al. Hum. Mutat., 2007 Jun;28:599-612; Ponti G et al. Hered Cancer Clin Pract, 2011 Aug;9:6). In addition, another different nucleotide change at the same position (c.479G>T) occurred de novo in an individual meeting NF1 diagnostic criteria (Bianchessi D et al. Mol Genet Genomic Med, 2015 Nov;3:513-25; Leiden Open Variation Database- http:// www.LOVD.nl/NF1). This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site; however, direct evidence is unavailable. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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