Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000217294 | SCV000277618 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-08-09 | criteria provided, single submitter | clinical testing | The p.V1609A variant (also known as c.4826T>C), located in coding exon 36 of the NF1 gene, results from a T to C substitution at nucleotide position 4826. The valine at codon 1609 is replaced by alanine, an amino acid with 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 6499 samples (12998 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 55,000alleles tested) in our clinical cohort.This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive.<span style="font-family:arial,sans-serif; font-size:9pt">Since supporting evidence is limited at this time, the clinical significance of p.V1609A<span style="font-family:arial,sans-serif; font-size:9pt"> remains unclear. |
| Labcorp Genetics |
RCV003495123 | SCV004329270 | uncertain significance | Neurofibromatosis, type 1 | 2023-10-27 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1588 of the NF1 protein (p.Val1588Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 233275). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NF1 protein function. 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. |