Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Center for Human Genetics, |
RCV000659972 | SCV000781886 | pathogenic | Neurofibromatosis, type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV000757560 | SCV000885846 | uncertain significance | not provided | 2017-12-03 | criteria provided, single submitter | clinical testing | The NF1 c.980T>C; p.Leu327Pro variant is published in the medical literature in one individual with a clinical diagnosis of NF1 (Syrbe 2007). Additionally, other variants in the same codon, p.Leu327Gln and p.Leu327Arg, are described in a gene-specific database (see link below). The p.Leu327Pro variant is not described in the ClinVar database, or in the general population-based databases, but is listed in the dbSNP variant database (rs201624827). The leucine at this position is well conserved across species and computational algorithms (PolyPhen2, SIFT) predict this variant is deleterious. Considering available information, there is insufficient evidence to classify this variant with certainty. References: Link to NF1 database: https://databases.lovd.nl/shared/genes/NF1 Syrbe S et al. Neurofibromatosis type 1 and associated clinical abnormalities in 27 children. Klin Padiatr. 2007 Nov-Dec;219(6):326-32. |
| Invitae | RCV000659972 | SCV000931036 | uncertain significance | Neurofibromatosis, type 1 | 2023-03-11 | 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. 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: 547576). This missense change has been observed in individual(s) with neurofibromatosis type 1 (PMID: 18183640, 29685074). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 327 of the NF1 protein (p.Leu327Pro). |
| Ambry Genetics | RCV002369783 | SCV002689598 | likely pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-03-29 | criteria provided, single submitter | clinical testing | The p.L327P variant (also known as c.980T>C), located in coding exon 9 of the NF1 gene, results from a T to C substitution at nucleotide position 980. The leucine at codon 327 is replaced by proline, an amino acid with similar properties. This alteration has been determined to be the result of a de novo event in one individual in our laboratory. This variant has been reported in an individual with neurofibromatosis type 1 (Syrbe S et al. Klin Padiatr. 2007; 219:326-32). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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 majority of available evidence to date, this variant is likely to be pathogenic. |