ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.1585C>T (p.Leu529Phe)

dbSNP: rs1135402816
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Medical Genetics, University of Parma RCV000497216 SCV000588728 likely pathogenic Neurofibromatosis, type 1 2022-08-17 criteria provided, single submitter clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV000497216 SCV002061881 likely pathogenic Neurofibromatosis, type 1 2021-06-04 criteria provided, single submitter clinical testing PS4_Supporting, PP2, PP3, PM2, PM6
Labcorp Genetics (formerly Invitae), Labcorp RCV000497216 SCV004539027 likely pathogenic Neurofibromatosis, type 1 2023-07-28 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NF1 protein function. ClinVar contains an entry for this variant (Variation ID: 431592). This missense change has been observed in individual(s) with neurofibromatosis type I (PMID: 28961165; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 529 of the NF1 protein (p.Leu529Phe).
Ambry Genetics RCV004559129 SCV005048110 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2024-02-09 criteria provided, single submitter clinical testing The p.L529F variant (also known as c.1585C>T), located in coding exon 14 of the NF1 gene, results from a C to T substitution at nucleotide position 1585. The leucine at codon 529 is replaced by phenylalanine, an amino acid with highly similar properties. This alteration was identified in an individual with a clinical diagnosis of neurofibromatosis type 1 (NF1) (Bonatti F et al. Int J Mol Sci, 2017 Sep;18:). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.

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