ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1753C>T (p.His585Tyr)

dbSNP: rs1401332173
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001213634 SCV001385276 uncertain significance Retinoblastoma 2023-03-01 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 585 of the RB1 protein (p.His585Tyr). This variant is present in population databases (no rsID available, gnomAD no frequency). This missense change has been observed in individual(s) with retinoblastoma (PMID: 12541220). ClinVar contains an entry for this variant (Variation ID: 943445). 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) performed at Invitae indicates that this missense variant is not expected to disrupt 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.
Mendelics RCV002249802 SCV002519259 uncertain significance not specified 2022-05-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV002411788 SCV002716561 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-29 criteria provided, single submitter clinical testing The p.H585Y variant (also known as c.1753C>T), located in coding exon 18 of the RB1 gene, results from a C to T substitution at nucleotide position 1753. The histidine at codon 585 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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