Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV003172327 | SCV003861612 | likely pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-12-21 | criteria provided, single submitter | clinical testing | The c.4269+1dupG intronic variant results from a duplication of one nucleotide after coding exon 31 of the NF1 gene. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |