Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000227710 | SCV000284389 | pathogenic | Neurofibromatosis, type 1 | 2021-05-12 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Leu532 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This variant has been observed in individual(s) with clinical features of neurofibromatosis (PMID: 30014477, 31370276, Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 237521). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with arginine at codon 532 of the NF1 protein (p.Leu532Arg). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and arginine. |
| Ambry Genetics | RCV002399810 | SCV002709021 | likely pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2018-05-03 | criteria provided, single submitter | clinical testing | The p.L532R variant (also known as c.1595T>G), located in coding exon 14 of the NF1 gene, results from a T to G substitution at nucleotide position 1595. The leucine at codon 532 is replaced by arginine, an amino acid with dissimilar properties. This variant was detected in an individual meeting diagnostic criteria for neurofibromatosis type I (NF1) in our laboratory (Ambry internal data). A different amino acid substitution at the same codon (p.L532P) was also identified in an patient affected with NF1 (Mattocks C et al. J. Med. Genet., 2004 Apr;41:e48). 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. |
| Baylor Genetics | RCV003469141 | SCV004190798 | likely pathogenic | Juvenile myelomonocytic leukemia | 2022-07-19 | criteria provided, single submitter | clinical testing |