Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002027081 | SCV002311178 | uncertain significance | Retinoblastoma | 2023-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 507 of the RB1 protein (p.Asp507His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1517078). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RB1 protein function. 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. |
Sema4, |
RCV002256892 | SCV002530796 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-08 | criteria provided, single submitter | curation | |
Ambry Genetics | RCV002256892 | SCV002708150 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-22 | criteria provided, single submitter | clinical testing | The p.D507H variant (also known as c.1519G>C), located in coding exon 17 of the RB1 gene, results from a G to C substitution at nucleotide position 1519. The aspartic acid at codon 507 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Laboratory of Molecular Epidemiology of Birth Defects, |
RCV003154233 | SCV003843667 | likely pathogenic | Ovarian cancer | 2022-01-01 | criteria provided, single submitter | clinical testing |