Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000165347 | SCV000216071 | uncertain significance | Hereditary cancer-predisposing syndrome | 2014-08-15 | criteria provided, single submitter | clinical testing | ​<span style="background-color: initial;">The <strong style="background-color: initial;">p.A761P<span style="background-color: initial;"> variant (also known as c.2281G>C), located in coding exon 19 of the<em style="background-color: initial;"> NF1 <span style="background-color: initial;">gene, results from a G to C substitution at nucleotide position 2281. The alanine at codon 761 is replaced by proline, 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 0.01% (greater than 11000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be benign and deleterious by PolyPhen and SIFT<em style="background-color: initial;"> in silico<span style="background-color: initial;"> analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of p.A761P remains unclear. |
| Labcorp Genetics |
RCV000809149 | SCV000949290 | uncertain significance | Neurofibromatosis, type 1 | 2018-11-06 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with NF1-related disease. ClinVar contains an entry for this variant (Variation ID: 185850). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with proline at codon 761 of the NF1 protein (p.Ala761Pro). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and proline. |
| Genome- |
RCV000809149 | SCV002562022 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing |