Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000632463 | SCV000753648 | likely pathogenic | Neurofibromatosis, type 1 | 2020-09-21 | criteria provided, single submitter | clinical testing | 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. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with neurofibromatosis type 1 (PMID: 23656349, Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 527558). This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with proline at codon 2084 of the NF1 protein (p.His2084Pro). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and proline. |
Gene |
RCV002279454 | SCV002567741 | uncertain significance | not provided | 2022-02-16 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with neurofibromatosis type 1 (van Minkelen 2014); This variant is associated with the following publications: (PMID: 23656349) |