Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000706936 | SCV000836011 | uncertain significance | Adams-Oliver syndrome 5 | 2018-06-28 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with NOTCH1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with serine at codon 1413 of the NOTCH1 protein (p.Arg1413Ser). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and serine. |
Ambry Genetics | RCV002332514 | SCV002630463 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-05-09 | criteria provided, single submitter | clinical testing | The p.R1413S variant (also known as c.4237C>A), located in coding exon 25 of the NOTCH1 gene, results from a C to A substitution at nucleotide position 4237. The arginine at codon 1413 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |