Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Human Genetics, |
RCV000660032 | SCV000781979 | likely pathogenic | Neurofibromatosis, type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000660032 | SCV002195817 | pathogenic | Neurofibromatosis, type 1 | 2021-10-29 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with NF1-related conditions. This sequence change creates a premature translational stop signal (p.Lys1105*) in the NF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 547625). 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. |
Genome- |
RCV000660032 | SCV002559948 | pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004993919 | SCV005459485 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2024-10-16 | criteria provided, single submitter | clinical testing | The p.K1105* pathogenic mutation (also known as c.3313A>T), located in coding exon 25 of the NF1 gene, results from an A to T substitution at nucleotide position 3313. This changes the amino acid from a lysine to a stop codon within coding exon 25. This variant has been observed in at least one individual with a personal and/or family history that is consistent with neurofibromatosis type 1 (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |