Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000033266 | SCV000057171 | uncertain significance | not provided | 2015-08-10 | criteria provided, single submitter | clinical testing | The P14R missense substitution has not been published as a mutation or as a benign polymorphism to our knowledge. The P14R amino acid substitution is considered to be non-conservative as a neutral, polar Proline is being replaced by a basic, polar Arginine. In addition, the NHLBI ESP Exome Variant Server reports P14R was not observed in approximately 2000 control samples from individuals of European and African American backgrounds, indicating it is unlikely to be a common benign variant. However, this position is not highly conserved in this or related genes and is extremely variable in other species. Therefore, the interpretation of the pathogenicity of P14R is dependent upon the phenotype of the parent who harbors the variant. The variant is found in NOONAN panel(s). |
Invitae | RCV000654946 | SCV000776854 | uncertain significance | RASopathy | 2023-12-06 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 14 of the BRAF protein (p.Pro14Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRAF-related conditions. ClinVar contains an entry for this variant (Variation ID: 40334). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is not expected to disrupt BRAF function with a negative 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. |