Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000480683 | SCV000568602 | likely pathogenic | not provided | 2021-06-04 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 16199547, 27838393, 16944272, 20655465, 17879440, 27390349, 28862263, 27535533, 25486365, 31766501, 31370276, 27322474, 24803665, 31717729) |
| Invitae | RCV000632424 | SCV000753604 | pathogenic | Neurofibromatosis, type 1 | 2023-06-22 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 420076). 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. For these reasons, this variant has been classified as Pathogenic. This missense change has been observed in individual(s) with neurofibromatosis type 1 (PMID: 16944272, 27322474, 27838393). In at least one individual the variant was observed to be de novo. This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 553 of the NF1 protein (p.His553Arg). This variant is not present in population databases (gnomAD no frequency). |
| Center for Human Genetics, |
RCV000632424 | SCV000781925 | pathogenic | Neurofibromatosis, type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
| Genome- |
RCV000632424 | SCV002561687 | likely pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002402394 | SCV002706043 | likely pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-09-19 | criteria provided, single submitter | clinical testing | The p.H553R variant (also known as c.1658A>G), located in coding exon 15 of the NF1 gene, results from an A to G substitution at nucleotide position 1658. The histidine at codon 553 is replaced by arginine, an amino acid with highly similar properties. This alteration has been observed in multiple individuals with a personal and/or family history that is consistent with NF1-related disease (Ambry internal data; Yao R et al. Genes (Basel), 2019 10;10; Demir Gündoan B et al. Turk J Med Sci, 2021 Aug). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |