Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000658393 | SCV000780165 | uncertain significance | not provided | 2018-05-31 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the NOTCH1 gene. The R1356C variant has been published in one European individual from a cohort of individuals with no known personal or family history indicative of a cancer predisposition syndrome who underwent whole genome sequencing (Bodian et al., 2014), although additional clinical details unrelated to cancer history were not described. The R1356C variant is also not observed in large population cohorts (Lek et al., 2016). The R1356C variant 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. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. However, this variant has not been observed in a significant number of affected individuals, and it lacks both segregation and functional studies which would further clarify its pathogenicity. |
Invitae | RCV001201674 | SCV001372756 | likely benign | Adams-Oliver syndrome 5 | 2023-05-15 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001201674 | SCV002553439 | uncertain significance | Adams-Oliver syndrome 5 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV002269858 | SCV002553440 | uncertain significance | Aortic valve disease 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004019690 | SCV004990173 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-12-30 | criteria provided, single submitter | clinical testing | The c.4066C>T (p.R1356C) alteration is located in exon 25 (coding exon 25) of the NOTCH1 gene. This alteration results from a C to T substitution at nucleotide position 4066, causing the arginine (R) at amino acid position 1356 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
ITMI | RCV000121683 | SCV000085881 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |