Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Human Genetics, |
RCV000660106 | SCV000782090 | likely pathogenic | Neurofibromatosis, type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Genome Diagnostics Laboratory, |
RCV000660106 | SCV001478960 | likely pathogenic | Neurofibromatosis, type 1 | 2020-10-26 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000660106 | SCV002271393 | likely pathogenic | Neurofibromatosis, type 1 | 2021-11-15 | 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant is associated with altered splicing, but the impact on the resulting protein product is unknown (PMID: 10862084, 27074763). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 547685). This variant is also known as c.6921G>A. This missense change has been observed in individual(s) with Neurofibromatosis, type 1 and/or NF1-related conditions (PMID: 10862084; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 2286 of the NF1 protein (p.Lys2286Asn). This variant also falls at the last nucleotide of exon 45, which is part of the consensus splice site for this exon. |
Genome- |
RCV000660106 | SCV002560220 | likely pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing |