Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000493470 | SCV000581865 | uncertain significance | not provided | 2019-01-08 | criteria provided, single submitter | clinical testing | The A624T variant of uncertain significance in the NOTCH1 gene has not been published as pathogenic or been reported as benign to our knowledge. This variant is observed in 5/23,728 (0.02%) alleles from individuals of African ancestry in large population cohorts (Lek et al., 2016). A624T 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. Additional evidence is needed to clarify the pathogenicity of this variant, including observation in a significant number of affected individuals, segregation data, and functional evidence.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign. |
Ambry Genetics | RCV002413355 | SCV002723504 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-04-04 | criteria provided, single submitter | clinical testing | The p.A624T variant (also known as c.1870G>A), located in coding exon 11 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 1870. The alanine at codon 624 is replaced by threonine, an amino acid with similar 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. |
Invitae | RCV003586189 | SCV004275184 | likely benign | Adams-Oliver syndrome 5 | 2023-11-14 | criteria provided, single submitter | clinical testing |