Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000037921 | SCV000061584 | likely pathogenic | Cardio-facio-cutaneous syndrome | 2012-02-29 | criteria provided, single submitter | clinical testing | The Ala481Glu variant has not been reported in the literature nor previously ide ntified by our laboratory. This variant was not identified in either parent of t his individual; therefore, the variant has likely occurred de novo in this indiv idual, assuming that non-medical explanations including alternate paternity or u ndisclosed adoption have been ruled out. Computational analyses (biochemical am ino acid properties, conservation, PolyPhen2, SIFT, AlignGVGD) suggest that the Ala481Gln variant may impact the protein. In addition, this variant occurs with in the functionally important ATP binding pocket of the BRAF tyrosine kinase dom ain. In summary, this variant is likely to be pathogenic although further studi es could help establish the pathogenicity of this variant. The presence of a he terozygous pathogenic variant in BRAF is consistent with a diagnosis of cardio-f acio-cutaneous syndrome but this information should be reconciled with the compl ete clinical history of this individual. |
| 3billion | RCV002051804 | SCV002318665 | likely pathogenic | Cardiofaciocutaneous syndrome 1 | 2022-03-22 | criteria provided, single submitter | clinical testing | Same nucleotide change resulting in same amino acid change has been previously reported to be associated with [GeneName] related disorder (ClinVar ID: VCV000044805, PMID:24800029). A different missense change at the same codon has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000636502). The variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.99>=0.6). A missense variant is a common mechanism . It is not observed in the gnomAD v2.1.1 dataset. Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| Centre de Biologie Pathologie Génétique, |
RCV002273942 | SCV002558933 | pathogenic | Neurodevelopmental delay | criteria provided, single submitter | clinical testing |