ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1964A>G (p.Tyr655Cys)

dbSNP: rs774196937
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001257132 SCV002267569 uncertain significance Retinoblastoma 2021-02-27 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with cysteine at codon 655 of the RB1 protein (p.Tyr655Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant has not been reported in the literature in individuals with RB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 978460). 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. 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 expected to disrupt RB1 protein function.
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan RCV001257132 SCV001432969 likely pathogenic Retinoblastoma 2019-05-09 no assertion criteria provided clinical testing

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