Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000233763 | SCV000290238 | benign | Adams-Oliver syndrome 5 | 2022-12-06 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001354684 | SCV001549360 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The NOTCH1 p.Cys359Cys variant was not identified in the literature nor was it identified in ClinVar or LOVD 3.0. The variant was identified in dbSNP (ID: rs202235419) and ClinVar (classified as a variant of uncertain significance by Invitae for Adams-Oliver syndrome 5). The variant was identified in control databases in 5 of 246920 chromosomes at a frequency of 0.00002025 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: East Asian in 3 of 18082 chromosomes (freq: 0.000166), South Asian in 1 of 30592 chromosomes (freq: 0.000033) and Latino in 1 of 34456 chromosomes (freq: 0.000029), but was not observed in the African, Ashkenazi Jewish, European (Finnish), European (non-Finnish), or Other populations. The p.Cys359Cys variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site, however 4 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing and the creation of a new 5' splice site. However, this has not been confirmed through RNA analysis and is not predictive enough to assume pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |