Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000817222 | SCV000957772 | pathogenic | Neurofibromatosis, type 1 | 2024-03-01 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 338 of the NF1 protein (p.Asp338Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of neurofibromatosis type I (PMID: 9298829, 30014477, 31730495, 33911094; Invitae). ClinVar contains an entry for this variant (Variation ID: 68297). 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 with a positive predictive value of 95%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV000059149 | SCV002599728 | likely pathogenic | not provided | 2022-11-04 | 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; In silico analysis supports a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 24803665, 9298829, 31730495, 33911094, Kamis2021[article], 30014477) |
Institute of Medical Genetics and Applied Genomics, |
RCV000817222 | SCV005045648 | likely pathogenic | Neurofibromatosis, type 1 | 2024-05-29 | criteria provided, single submitter | clinical testing | |
Uni |
RCV000059149 | SCV000090678 | not provided | not provided | no assertion provided | not provided |