Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000492435 | SCV000580863 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-09-01 | criteria provided, single submitter | clinical testing | The p.E237* pathogenic mutation (also known as c.709G>T), located in coding exon 7 of the RB1 gene, results from a G to T substitution at nucleotide position 709. This changes the amino acid from a glutamic acid to a stop codon within coding exon 7. This mutation has been detected in one individual with bilateral retinoblastoma (RB) and leukemia and was also detected in one individual from a cohort of patients with with either bilateral and/or familial RB or unilateral sporadic RB (Barbosa RH, et al. Invest. Ophthalmol. Vis. Sci. 2013; 54(5):3184-94, Price EA, et al. J. Med. Genet. 2014; 51(3):208-14). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Labcorp Genetics |
RCV003514369 | SCV004297214 | pathogenic | Retinoblastoma | 2023-07-16 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 428731). This premature translational stop signal has been observed in individual(s) with retinoblastoma (PMID: 23532519, 24225018). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu237*) in the RB1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RB1 are known to be pathogenic (PMID: 17096365). |