ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.722C>T (p.Thr241Ile)

dbSNP: rs1593445085
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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 RCV001026182 SCV001188510 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-05 criteria provided, single submitter clinical testing The p.T241I variant (also known as c.722C>T), located in coding exon 8 of the RB1 gene, results from a C to T substitution at nucleotide position 722. The threonine at codon 241 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is highly conserved through mammalian species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001873406 SCV002166517 uncertain significance Retinoblastoma 2021-09-07 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals affected with RB1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with isoleucine at codon 241 of the RB1 protein (p.Thr241Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine.
All of Us Research Program, National Institutes of Health RCV001873406 SCV004844624 uncertain significance Retinoblastoma 2023-03-23 criteria provided, single submitter clinical testing This missense variant replaces threonine with isoleucine at codon 241 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 not been reported in individuals affected with RB1-related disorders in the literature. This variant has not been identified 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.

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