Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Medical Genetics, |
RCV000497149 | SCV000588799 | likely pathogenic | Neurofibromatosis, type 1 | 2022-08-17 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000497149 | SCV001541863 | likely pathogenic | Neurofibromatosis, type 1 | 2021-08-27 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NF1 protein function. This variant has been observed in individual(s) with neurofibromatosis type 1 (PMID: 28961165). ClinVar contains an entry for this variant (Variation ID: 431655). This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with aspartic acid at codon 1805 of the NF1 protein (p.His1805Asp). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and aspartic acid. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003235254 | SCV003934413 | uncertain significance | not specified | 2023-05-30 | criteria provided, single submitter | clinical testing | Variant summary: NF1 c.5413C>G (p.His1805Asp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251382 control chromosomes. c.5413C>G has been reported as de novo in the literature in individuals affected with Neurofibromatosis Type 1 (Bonatti_2017). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 28961165). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |