Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000474130 | SCV000559902 | likely benign | Adams-Oliver syndrome 5 | 2019-12-31 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000121687 | SCV000569024 | uncertain significance | not specified | 2017-03-09 | criteria provided, single submitter | clinical testing | The R1350L variant was first reported in a 70-year-old individual with a personal and family history of bicuspid aortic valve disease and thoracic aortic aneurysm, who also harbored a second missense variant in the NOTCH1 gene (McKellar at al., 2007). The R1350L variant has also been identified in a European American individual with aortic valve stenosis (McBride et al., 2008). However, no segregation studies were described in either of these publications. Kerstjens-Frederikse et al. (2016) subsequently reported R1350L in three individuals from a cohort of 428 Dutch individuals with non-syndromic left-sided congenital heart defects, and their individual phenotypes included hypoplastic left heart syndrome, coarctation of the aorta, and interruption of the aorta with a ventricular septal defect. In two of these cases, where parental testing was performed, R1350L was inherited from a father with a normal echocardiogram (Kerstjens-Frederikse et al., 2016).The R1350L 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. Moreover, this substitution occurs at a position that is conserved in mammals. Nevertheless, in silico analysis predicts this variant likely does not alter the protein structure/function. Furthermore, the R1350L variant has been observed in 54/48172 (0.11%) alleles from individuals of Non-Finnish European ancestry in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Additionally, this variant has been reported in other small control populations at a frequency of approximately 0.07-0.53% (McKellar et al., 2007; McBride et al., 2008; Bodian et al., 2014). |
Ambry Genetics | RCV000621899 | SCV000739359 | likely benign | Cardiovascular phenotype | 2019-01-09 | criteria provided, single submitter | clinical testing | In silico models in agreement (benign);No disease association in small case-control study |
Center for Human Genetics, |
RCV000680588 | SCV000808012 | likely benign | Connective tissue disease | 2018-06-01 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV000770629 | SCV000902080 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2016-04-21 | criteria provided, single submitter | clinical testing | |
ITMI | RCV000121687 | SCV000085885 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |