Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000220178 | SCV000275512 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-05-04 | criteria provided, single submitter | clinical testing | The p.L658F variant (also known as c.1972C>T), located in coding exon 17 of the NF1 gene, results from a C to T substitution at nucleotide position 1972. The leucine at codon 658 is replaced by phenylalanine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 55000 alleles tested) in our clinical cohort. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of p.L658F remains unclear. |
| Labcorp Genetics |
RCV000466869 | SCV000542203 | benign | Neurofibromatosis, type 1 | 2024-11-18 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001557652 | SCV001779448 | likely benign | not provided | 2019-08-30 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV004558518 | SCV005048598 | likely benign | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-06-01 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |