Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000482168 | SCV000574227 | uncertain significance | not provided | 2017-11-22 | criteria provided, single submitter | clinical testing | The I326T variant of uncertain significance in the BRAF gene has not been published as pathogenic in association with cardiomyopathy or been reported as benign to our knowledge. The I326T variant is observed in 4/24034 (0.02%) alleles from individuals of African background in large population cohorts (Lek et al., 2016). This variant has also been identified in conjunction with additional cardiogenetic variants in one other individual referred for cardiac genetic testing at GeneDx; however, thus far, segregation data is limited or absent due to the lack of clinical information provided and/or insufficient participation by informative family members. The I326T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. |
| Labcorp Genetics |
RCV001851275 | SCV002149171 | uncertain significance | RASopathy | 2025-01-12 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 326 of the BRAF protein (p.Ile326Thr). This variant is present in population databases (rs368435578, gnomAD 0.02%). 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: 424419). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BRAF protein 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. |
| Service de Génétique Moléculaire, |
RCV001261042 | SCV001438443 | uncertain significance | Noonan syndrome | no assertion criteria provided | clinical testing |