Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001296871 | SCV001485848 | uncertain significance | Neurofibromatosis, type 1 | 2017-12-31 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with NF1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with tyrosine at codon 2794 of the NF1 protein (p.His2794Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. |
Ambry Genetics | RCV004557510 | SCV005048877 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2024-02-20 | criteria provided, single submitter | clinical testing | The p.H2794Y variant (also known as c.8380C>T), located in coding exon 57 of the NF1 gene, results from a C to T substitution at nucleotide position 8380. The histidine at codon 2794 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. |