Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV003172309 | SCV003861582 | likely pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-11-30 | criteria provided, single submitter | clinical testing | The p.Q270P variant (also known as c.809A>C), located in coding exon 8 of the NF1 gene, results from an A to C substitution at nucleotide position 809. The glutamine at codon 270 is replaced by proline, an amino acid with similar properties. This alteration was identified in multiple patients with a confirmed or suspected clinical diagnosis of neurofibromatosis type 1 (Pasmant E et al. Eur J Hum Genet. 2015 May;23:596-601; Kang E et al. J Hum Genet. 2020 Jan;65:79-89; Ambry internal data). 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. |
| Gene |
RCV003318752 | SCV004022853 | likely pathogenic | not provided | 2023-08-29 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25074460, 31776437) |
| Labcorp Genetics |
RCV003598152 | SCV004376676 | likely pathogenic | Neurofibromatosis, type 1 | 2023-06-09 | 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: 2452215). This missense change has been observed in individuals with neurofibromatosis type I (PMID: 31776437; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 270 of the NF1 protein (p.Gln270Pro). |
| NHS Central & South Genomic Laboratory Hub | RCV003598152 | SCV005393953 | likely pathogenic | Neurofibromatosis, type 1 | 2024-11-11 | criteria provided, single submitter | clinical testing |