Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000632350 | SCV000753528 | uncertain significance | Neurofibromatosis, type 1 | 2021-03-11 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glutamic acid at codon 1060 of the NF1 protein (p.Asp1060Glu). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 527474). 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 not expected to disrupt NF1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
ARUP Laboratories, |
RCV001811126 | SCV002050130 | uncertain significance | not provided | 2021-10-14 | criteria provided, single submitter | clinical testing | The NF1 c.3180T>G; p.Asp1060Glu variant (rs1555614646) to our knowledge, is not reported in the medical literature but is reported in a gene-specific database (see link below) and in the ClinVar database (Variation ID: 527474). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The aspartic acid at codon 1060 is highly conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.179). Due to limited information, the clinical significance of the p.Asp1060Glu variant is uncertain at this time. References: Link to NF1 database: https://databases.lovd.nl/shared/genes/NF1 |
Genome- |
RCV000632350 | SCV002560271 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing |