Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002313740 | SCV000663207 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-11-22 | criteria provided, single submitter | clinical testing | The p.H31R variant (also known as c.92A>G), located in coding exon 2 of the NF1 gene, results from an A to G substitution at nucleotide position 92. The histidine at codon 31 is replaced by arginine, an amino acid with highly similar properties. This alteration was identified in 1/91 probands fulfilling the NIH diagnostic criteria for neurofibromatosis type 1 (NF1) (Mattocks C et al. J. Med. Genet., 2004 Apr;41:e48). Another study that assessed missense mutations by combining protein network data with mutational analyses based on 3D structures using the protein design algorithm FoldX found this alteration to have no effect (Kiel C et al. Mol. Syst. Biol., 2014 May;10:727). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. |
| Labcorp Genetics |
RCV001854237 | SCV002223061 | uncertain significance | Neurofibromatosis, type 1 | 2024-11-15 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 31 of the NF1 protein (p.His31Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of neurofibromatosis type 1 (PMID: 15060124; internal data). ClinVar contains an entry for this variant (Variation ID: 68364). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NF1 protein function. 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. |
| Genome- |
RCV001854237 | SCV002561403 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Uni |
RCV000059218 | SCV000090747 | not provided | not provided | no assertion provided | not provided |