ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1313G>A (p.Cys438Tyr)

dbSNP: rs1952832267
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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 RCV001203708 SCV001374884 uncertain significance Retinoblastoma 2023-12-18 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 438 of the RB1 protein (p.Cys438Tyr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 935171). 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 with a negative predictive value of 80%. 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.
Ambry Genetics RCV002379771 SCV002691675 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-02 criteria provided, single submitter clinical testing The p.C438Y variant (also known as c.1313G>A), located in coding exon 13 of the RB1 gene, results from a G to A substitution at nucleotide position 1313. The cysteine at codon 438 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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.
All of Us Research Program, National Institutes of Health RCV001203708 SCV004825064 uncertain significance Retinoblastoma 2023-08-15 criteria provided, single submitter clinical testing

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