Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000489444 | SCV000577244 | likely pathogenic | not provided | 2023-03-28 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25486365, 2121369, 30274822, 32579932, 25326804, 26689913, 31925297, 27397505, 30287823, 30981987) |
| Labcorp Genetics |
RCV000540077 | SCV000628479 | likely pathogenic | Neurofibromatosis, type 1 | 2024-05-31 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 997 of the NF1 protein (p.Arg997Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of NF1-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 426719). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Genome- |
RCV000540077 | SCV002561822 | likely pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000489444 | SCV005624556 | likely pathogenic | not provided | 2024-10-18 | criteria provided, single submitter | clinical testing | The NF1 c.2991G>T (p.Arg997Ser) variant disrupts a canonical splice-acceptor site and is predicted to interfere with normal NF1 mRNA splicing. This variant has not been reported in individuals with NF1-related conditions in the published literature. This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as likely pathogenic. |