ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.2186A>C (p.Lys729Thr)

gnomAD frequency: 0.00001  dbSNP: rs150600740
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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 RCV001919842 SCV002160935 uncertain significance Retinoblastoma 2021-11-26 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with RB1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 729 of the RB1 protein (p.Lys729Thr).
Ambry Genetics RCV002425194 SCV002730149 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-28 criteria provided, single submitter clinical testing The p.K729T variant (also known as c.2186A>C), located in coding exon 21 of the RB1 gene, results from an A to C substitution at nucleotide position 2186. The lysine at codon 729 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. 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.
All of Us Research Program, National Institutes of Health RCV001919842 SCV004844724 uncertain significance Retinoblastoma 2023-03-09 criteria provided, single submitter clinical testing This missense variant replaces lysine with threonine at codon 729 of the RB1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer 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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