ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.34A>T (p.Thr12Ser)

gnomAD frequency: 0.00001  dbSNP: rs1566174063
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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 RCV000703761 SCV000832676 uncertain significance Retinoblastoma 2023-01-10 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 12 of the RB1 protein (p.Thr12Ser). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RB1 protein function. ClinVar contains an entry for this variant (Variation ID: 580275). This variant has not been reported in the literature in individuals affected with RB1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%).
Ambry Genetics RCV001020458 SCV001181942 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-27 criteria provided, single submitter clinical testing The p.T12S variant (also known as c.34A>T), located in coding exon 1 of the RB1 gene, results from an A to T substitution at nucleotide position 34. The threonine at codon 12 is replaced by serine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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