Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002319417 | SCV001185851 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2019-03-28 | criteria provided, single submitter | clinical testing | The p.C1771* pathogenic mutation (also known as c.5313C>A), located in coding exon 37 of the NF1 gene, results from a C to A substitution at nucleotide position 5313. This changes the amino acid from a cysteine to a stop codon within coding exon 37. In addition to the clinical data presented in the literature, 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002271610 | SCV002555665 | likely pathogenic | Neurofibromatosis, type 1 | 2022-06-06 | criteria provided, single submitter | clinical testing | Variant summary: NF1 c.5313C>A (p.Cys1771X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251404 control chromosomes. To our knowledge, no occurrence of c.5313C>A in individuals affected with Neurofibromatosis Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |