ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1814T>C (p.Met605Thr)

dbSNP: rs1555293654
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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 RCV000529955 SCV000629294 uncertain significance Retinoblastoma 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 605 of the RB1 protein (p.Met605Thr). 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: 458137). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 RCV002413464 SCV002716486 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-27 criteria provided, single submitter clinical testing The c.1814T>C variant (also known as p.M605T), located in coding exon 18 of the RB1 gene, results from a T to C substitution at nucleotide position 1814. The amino acid change results in methionine to threonine at codon 605, an amino acid with similar properties. This change occurs in the last base pair of coding exon 18. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
All of Us Research Program, National Institutes of Health RCV000529955 SCV004841374 uncertain significance Retinoblastoma 2023-10-23 criteria provided, single submitter clinical testing This missense variant replaces methionine with threonine at codon 605 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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