Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001990976 | SCV002261260 | uncertain significance | Neurofibromatosis, type 1 | 2023-04-16 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with NF1-related conditions. This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 464 of the NF1 protein (p.Pro464Gln). This variant is present in population databases (no rsID available, gnomAD 0.007%). ClinVar contains an entry for this variant (Variation ID: 1479552). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Ambry Genetics | RCV004558779 | SCV005047490 | likely benign | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-04-07 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |