Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000370641 | SCV000367761 | likely benign | Noonan-like syndrome | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000593984 | SCV000709708 | uncertain significance | not specified | 2018-03-06 | criteria provided, single submitter | clinical testing | Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 2 /126572 Europeans in GnomAd; not in HGMD or google search; likely benign by Illumina in ClinVar, conserved, predicted benign. Identified in 1 individual with HCM. |
Labcorp Genetics |
RCV001850605 | SCV002292124 | uncertain significance | RASopathy | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 454 of the CBL protein (p.Asn454Asp). This variant is present in population databases (rs371850672, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with CBL-related conditions. ClinVar contains an entry for this variant (Variation ID: 302780). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CBL protein function with a negative predictive value of 95%. 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. |