Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000037910 | SCV000061572 | uncertain significance | not specified | 2011-10-20 | criteria provided, single submitter | clinical testing | The Val413Met variant has not been reported in the literature nor identified by our laboratory in over 1,300 individuals. Valine (Val) at position 413 is highly conserved across evolutionarily distant species, suggesting that a change to th e amino acid may not be tolerated. Computational analyses (PolyPhen2, SIFT, Ali gnGVGD) do not provide strong support for or against pathogenicity; however, the accuracy of these tools is unknown. In the absence of additional information, s uch as control studies, segregation data, or functional analyses, the clinical s ignificance of this variant cannot be determined at this time. |
| Fulgent Genetics, |
RCV002477098 | SCV000895822 | uncertain significance | Cardiofaciocutaneous syndrome 1; Noonan syndrome 1; LEOPARD syndrome 3; Noonan syndrome 7; Melanoma, cutaneous malignant, susceptibility to, 1; Colorectal cancer; Lung cancer | 2021-12-06 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV001270774 | SCV001451526 | uncertain significance | Noonan syndrome 7 | 2019-02-14 | criteria provided, single submitter | clinical testing | The BRAF c.1237G>A (p.Val413Met) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is found at a frequency of 0.000033 in the South Asian population of the Genome Aggregation Database, but this is based on one allele only in a region of good sequence coverage so the variant is presumed to be rare. Based on the limited evidence, the p.Val413Met variant is classified as a variant of uncertain significance for Noonan syndrome. |
| Labcorp Genetics |
RCV002513488 | SCV002935318 | uncertain significance | RASopathy | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 413 of the BRAF protein (p.Val413Met). This variant is present in population databases (rs377093637, gnomAD 0.003%). 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: 44799). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BRAF protein function. 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. |