Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV004560861 | SCV005048881 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-10-25 | criteria provided, single submitter | clinical testing | The p.K395T variant (also known as c.1184A>C), located in coding exon 10 of the NF1 gene, results from an A to C substitution at nucleotide position 1184. The lysine at codon 395 is replaced by threonine, 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 deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV005100855 | SCV005779994 | uncertain significance | Neurofibromatosis, type 1 | 2024-09-03 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 395 of the NF1 protein (p.Lys395Thr). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |