Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000489937 | SCV000576602 | likely pathogenic | not provided | 2017-04-26 | criteria provided, single submitter | clinical testing | The c.7256_7258delCAG variant has been reported previously in association with neurofibromatosis type 1 (Pasmant et al., 2015). The deletion results in an in-frame deletion of the conserved Alanine at residue 2420, denoted p.Ala2420del. In silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, this codon is the final codon of exon 48, and the deletion of these nucleotides may have an effect on splicing. However, in silico splice prediction models are inconsistent in their predictions as to whether or not the variant is damaging to the splice donor site. The variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). In summary, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
Genome Diagnostics Laboratory, |
RCV001290811 | SCV001478970 | likely pathogenic | Neurofibromatosis, type 1 | 2020-10-26 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001290811 | SCV004296806 | uncertain significance | Neurofibromatosis, type 1 | 2024-10-29 | criteria provided, single submitter | clinical testing | This variant, c.7256_7258del, results in the deletion of 1 amino acid(s) of the NF1 protein (p.Ala2420del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with neurofibromatosis type 1 (PMID: 25074460). ClinVar contains an entry for this variant (Variation ID: 426216). 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. |