Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000229118 | SCV000284475 | uncertain significance | Neurofibromatosis, type 1 | 2024-01-09 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1722 of the NF1 protein (p.Ala1722Pro). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with midaortic syndrome (PMID: 29483232). ClinVar contains an entry for this variant (Variation ID: 237573). 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) performed at Invitae indicates that this missense variant is expected to disrupt NF1 protein function with a positive predictive value of 95%. 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. |
Ambry Genetics | RCV002318968 | SCV001185555 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-02-28 | criteria provided, single submitter | clinical testing | The p.A1722P variant (also known as c.5164G>C), located in coding exon 36 of the NF1 gene, results from a G to C substitution at nucleotide position 5164. The alanine at codon 1722 is replaced by proline, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Genome- |
RCV000229118 | SCV002560525 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Yale Center for Mendelian Genomics, |
RCV000845194 | SCV000987130 | likely pathogenic | Atypical coarctation of aorta | 2018-02-26 | no assertion criteria provided | literature only |