Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000492684 | SCV000580798 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-01-24 | criteria provided, single submitter | clinical testing | The c.-198G>A pathogenic mutation is located in the 5' untranslated region (5’ UTR) of the RB1 gene. This pathogenic mutation results from a G to A substitution 198 bases upstream from the first translated codon. In one study, c.-198G>A was determined to segregate with disease in a family with hereditary retinoblastoma. In addition, these authors demonstrated that the alteration interfered with binding of an essential RB1 transcription factor. Of note, multiple unaffected individuals were determined to carry the alteration, suggesting reduced penetrance (Sakai T et al. Nature. 1991;353(6339):83-6). This mutation has also been described in a patient presenting with unilateral retinoblastoma at 18 months of age, who had no family history of retinoblastoma (Pradhan MA et al. Clin. Experiment. Ophthalmol. 2010;38(3):231-6) and as a de novo alteration in a male individual presenting with unilateral retinoblastoma at 15 months of age ( Zajaczek S, et al. Eur. J. Cancer 1998 Nov; 34(12):1919-21). Based on nucleotide sequence alignment, this position is highly conserved in vertebrate species. Based on the supporting evidence, c.-198G>A is interpreted as a disease-causing mutation exhibiting reduced penetrance. |
| Labcorp Genetics |
RCV000013961 | SCV001580876 | pathogenic | Retinoblastoma | 2023-02-01 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 13086). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects RB1 function (PMID: 1881452). For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with retinoblastoma (PMID: 1881452, 10673998, 20447117). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This variant occurs in a non-coding region of the RB1 gene. It does not change the encoded amino acid sequence of the RB1 protein. This variant is not present in population databases (gnomAD no frequency). |
| Genetic Diagnostic Laboratory, |
RCV000013961 | SCV005046374 | pathogenic | Retinoblastoma | 2024-05-20 | criteria provided, single submitter | clinical testing | Case and Pedigree Information: BILATERAL CASES:1, UNILATERAL CASES:0, TOTAL CASES:1, PEDIGREES:1. ACMG Codes Applied:PS3, PM2, PS4SUP, PP5 |
| Department of Pathology and Laboratory Medicine, |
RCV000013961 | SCV005917437 | likely pathogenic | Retinoblastoma | criteria provided, single submitter | clinical testing | ||
| OMIM | RCV000013961 | SCV000034208 | pathogenic | Retinoblastoma | 1991-09-05 | no assertion criteria provided | literature only |