ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.643T>C (p.Ser215Pro)

gnomAD frequency: 0.00001  dbSNP: rs748923368
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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 RCV001025270 SCV001187428 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-16 criteria provided, single submitter clinical testing The p.S215P variant (also known as c.643T>C), located in coding exon 7 of the RB1 gene, results from a T to C substitution at nucleotide position 643. The serine at codon 215 is replaced by proline, an amino acid with similar properties. This amino acid position is highly 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001326894 SCV001517947 uncertain significance Retinoblastoma 2024-01-05 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 215 of the RB1 protein (p.Ser215Pro). This variant is present in population databases (rs748923368, gnomAD 0.02%). This missense change has been observed in individual(s) with breast cancer (PMID: 28580595). ClinVar contains an entry for this variant (Variation ID: 826406). 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. 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.
GeneDx RCV004721706 SCV005327165 uncertain significance not provided 2023-10-29 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23516486, 28580595, 32091409)

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