ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1505C>T (p.Thr502Ile)

gnomAD frequency: 0.00001  dbSNP: rs752334972
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000541847 SCV000629286 likely benign Retinoblastoma 2024-12-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV002395310 SCV002702402 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-26 criteria provided, single submitter clinical testing The p.T502I variant (also known as c.1505C>T), located in coding exon 17 of the RB1 gene, results from a C to T substitution at nucleotide position 1505. The threonine at codon 502 is replaced by isoleucine, 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.
All of Us Research Program, National Institutes of Health RCV000541847 SCV004844677 uncertain significance Retinoblastoma 2024-02-05 criteria provided, single submitter clinical testing This missense variant replaces threonine with isoleucine at codon 502 of the RB1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with breast cancer in the literature (PMID: 28202063). This variant has been identified in 1/241956 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx RCV004592554 SCV005081130 uncertain significance not provided 2023-12-04 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Observed in individuals with breast or other cancer history and has not been reported in individuals with RB1-related cancers to our knowledge (PMID: 35534704, 28202063); This variant is associated with the following publications: (PMID: 28202063, 35534704, 23516486, 31980996)

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