Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000706344 | SCV000835387 | uncertain significance | Neurofibromatosis, type 1 | 2022-02-20 | 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. This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 2609 of the NF1 protein (p.Thr2609Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 582304). 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 not expected to disrupt NF1 protein function. |
| Gene |
RCV001775978 | SCV002013813 | uncertain significance | not provided | 2020-03-11 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Genome- |
RCV000706344 | SCV002561153 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004559636 | SCV005048824 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-06-23 | criteria provided, single submitter | clinical testing | The p.T2609A variant (also known as c.7825A>G), located in coding exon 53 of the NF1 gene, results from an A to G substitution at nucleotide position 7825. The threonine at codon 2609 is replaced by alanine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |