Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000701091 | SCV000829874 | benign | Retinoblastoma | 2023-10-26 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000701091 | SCV001268039 | likely benign | Retinoblastoma | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
| Ambry Genetics | RCV002399489 | SCV002710024 | benign | Hereditary cancer-predisposing syndrome | 2022-09-29 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Laboratory of Molecular Epidemiology of Birth Defects, |
RCV003153399 | SCV003843657 | likely pathogenic | Ovarian cancer | 2022-01-01 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV000701091 | SCV004844682 | uncertain significance | Retinoblastoma | 2024-01-11 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with threonine at codon 525 of the RB1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with unilateral retinoblastoma but was also found in their unaffected parent and in other asymptomatic individuals (PMID: 24728327, 34680218). This variant has been identified in 15/249180 chromosomes in the general population by the Genome Aggregation Database (gnomAD), suggesting the variant frequency is greater than expected for the disease. The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Gene |
RCV004589589 | SCV005079000 | uncertain significance | not provided | 2023-08-15 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Observed in an individual with unilateral retinoblastoma as well as their unaffected parent (Alekseeva et al., 2021); Observed in an individual with stomach cancer, as well as healthy individuals undergoing whole genome sequencing (Bodian et al., 2014; Huang et al., 2018); This variant is associated with the following publications: (PMID: 24728327, 34680218, 36451132, 29625052) |
| ITMI | RCV000121919 | SCV000086124 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |