ClinVar Miner

Submissions for variant NM_000321.2(RB1):c.1436_1438ACA[1] (p.Asn480del) (rs587776788)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492635 SCV000580775 pathogenic Hereditary cancer-predisposing syndrome 2012-11-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Invitae RCV000013967 SCV000835651 likely pathogenic Retinoblastoma 2018-07-30 criteria provided, single submitter clinical testing This variant, c.1439_1441delACA, results in the deletion of 1 amino acid of the RB1 protein (p.Asn480del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with retinoblastoma in a family, though was carried by one unaffected family member (PMID: 7927327, 1577465). This variant has been reported as a germline change in an individual with familial unilateral retinoblastoma (PMID: 12541220) and in affected individuals in the Leiden Open-source Variation Database (PMID: 21520333). This This variant is also known as 1574del3 in the literature. ClinVar contains an entry for this variant (Variation ID: 13091). Experimental studies have shown that this missense change retains the ability to undergo cyclin-mediated phosphorylation but exhibits significantly reduced pocket-binding activity in a temperature-sensitive manner (PMID: 9342358, 10486322). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000013967 SCV000034214 pathogenic Retinoblastoma 1999-10-01 no assertion criteria provided literature only

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