Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001214947 | SCV001386657 | uncertain significance | Neurofibromatosis, type 1 | 2019-07-23 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with NF1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with histidine at codon 229 of the NF1 protein (p.Asp229His). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. |
Ambry Genetics | RCV002365965 | SCV002662860 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2021-07-06 | criteria provided, single submitter | clinical testing | The p.D229H variant (also known as c.685G>C), located in coding exon 7 of the NF1 gene, results from a G to C substitution at nucleotide position 685. The aspartic acid at codon 229 is replaced by histidine, 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. |