ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.479G>C (p.Arg160Thr)

dbSNP: rs199474752
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000538243 SCV000628622 pathogenic Neurofibromatosis, type 1 2022-03-08 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 4 and introduces a premature termination codon (PMID: 17311297). The resulting mRNA is expected to undergo nonsense-mediated decay. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 68353). This variant has been observed in individual(s) with Neurofibromatosis type I (NF1) (PMID: 17311297, 21838856; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects codon 160 of the NF1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NF1 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product.
Medical Genetics, University of Parma RCV000538243 SCV002567802 pathogenic Neurofibromatosis, type 1 2022-08-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV002336218 SCV002638376 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2018-09-18 criteria provided, single submitter clinical testing The c.479G>C pathogenic mutation (also known as p.R160T), located in coding exon 4 of the NF1 gene, results from a G to C substitution at nucleotide position 479. The amino acid change results in arginine to threonine at codon 160, an amino acid with 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 variant has been identified in patients meeting NIH diagnostic criteria for Neurofibromatosis type 1 (NF1) (Wimmer K et al. Hum. Mutat. 2007 Jun;28:599-612; Stella A et al. Genes (Basel) 2018 Apr;9(4)216). This mutation has also been reported in a patient with classic features of NF1 whose mother had breast cancer diagnosed at 59 (Ponti G et al. Hered Cancer Clin Pract 2011 Aug;9:6). Additionally, protein truncation testing (PTT) showed this variant results in skipping of exon 4 (Wimmer K et al. Hum. Mutat. 2007 Jun;28:599-612). Based on the available evidence, this variant is classified as a pathogenic mutation.
UniProtKB/Swiss-Prot RCV000059206 SCV000090735 not provided not provided no assertion provided not provided

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