Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002045406 | SCV002293207 | uncertain significance | Neurofibromatosis, type 1 | 2021-07-03 | 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. 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. This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with alanine at codon 567 of the NF1 protein (p.Val567Ala). The valine residue is weakly conserved and there is a small physicochemical difference between valine and alanine. |
Ambry Genetics | RCV002398092 | SCV002714150 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-08-23 | criteria provided, single submitter | clinical testing | The p.V567A variant (also known as c.1700T>C), located in coding exon 15 of the NF1 gene, results from a T to C substitution at nucleotide position 1700. The valine at codon 567 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. 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. |
Prevention |
RCV004553627 | SCV004117858 | uncertain significance | NF1-related disorder | 2022-11-30 | criteria provided, single submitter | clinical testing | The NF1 c.1700T>C variant is predicted to result in the amino acid substitution p.Val567Ala. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Gene |
RCV004779246 | SCV005389959 | uncertain significance | not provided | 2024-04-16 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25486365) |