Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000610566 | SCV000712243 | uncertain significance | not specified | 2016-10-18 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.Gly106Arg var iant in BRAF has been previously identified in 1 individual with clinical featur es of Noonan syndrome, but was also identified in an unaffected parent (LMM data ). It has been identified 1/66687 European and 1/16503 South Asian chromosomes b y the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs749247588). Computational prediction tools and conservation analysis suggest t hat the p.Gly106Arg variant may impact the protein, though this information is n ot predictive enough to determine pathogenicity. In summary, while the clinical significance of the p.Gly106Arg variant is uncertain, these data suggest that i t is more likely to be benign. |
| Labcorp Genetics |
RCV000794440 | SCV000933848 | uncertain significance | RASopathy | 2024-12-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 106 of the BRAF protein (p.Gly106Arg). This variant is present in population databases (rs749247588, gnomAD 0.006%). This missense change has been observed in individual(s) with neurofibromatosis type-1 (PMID: 30290804). ClinVar contains an entry for this variant (Variation ID: 505121). Invitae Evidence Modeling incorporating data from in vitro experimental studies (internal data) 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. |
| Illumina Laboratory Services, |
RCV001159564 | SCV001321283 | uncertain significance | LEOPARD syndrome 3 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| Illumina Laboratory Services, |
RCV001160943 | SCV001322782 | uncertain significance | Noonan syndrome 7 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| Mayo Clinic Laboratories, |
RCV004791619 | SCV005409388 | uncertain significance | not provided | 2024-08-29 | criteria provided, single submitter | clinical testing | BS4_supporting, PP2 |