Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000497105 | SCV001478609 | likely pathogenic | Neurofibromatosis, type 1 | 2021-01-28 | criteria provided, single submitter | clinical testing | Variant summary: NF1 c.2764G>A (p.Gly922Ser) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. Several computational tools predict a significant impact on normal splicing: Four predict the variant strengthens a cryptic exonic 5' splice donor site. At least one publication reports experimental evidence that this variant affects mRNA splicing (Ars_2003). The variant was absent in 251090 control chromosomes. c.2764G>A has been reported in the literature in at-least two individuals affected with some but not all diagnostic features of Neurofibromatosis Type 1 as well as in at-least one individual with a suspected diagnosis of Neurofibromatosis type 1 and also subsequently cited by others (example, Ars_2003, Pros_2008, Anastaski_2017, Bonatti_2017, Yoshida_2018). These data indicate that the variant may be associated with disease. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evalution and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Labcorp Genetics |
RCV000497105 | SCV001586754 | pathogenic | Neurofibromatosis, type 1 | 2025-01-17 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 922 of the NF1 protein (p.Gly922Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neurofibromatosis type 1 (PMID: 10607834, 28961165). ClinVar contains an entry for this variant (Variation ID: 431608). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt NF1 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
| Genome- |
RCV000497105 | SCV002561801 | likely pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Medical Genetics, |
RCV000497105 | SCV000588747 | uncertain significance | Neurofibromatosis, type 1 | 2017-02-02 | no assertion criteria provided | clinical testing |