ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.424A>G (p.Thr142Ala)

gnomAD frequency: 0.00001  dbSNP: rs1307149332
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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 RCV001360460 SCV001556377 uncertain significance Retinoblastoma 2022-07-17 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 1052305). This variant has not been reported in the literature in individuals affected with RB1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 142 of the RB1 protein (p.Thr142Ala).
Ambry Genetics RCV002329356 SCV002628675 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-20 criteria provided, single submitter clinical testing The p.T142A variant (also known as c.424A>G), located in coding exon 4 of the RB1 gene, results from an A to G substitution at nucleotide position 424. The threonine at codon 142 is replaced by alanine, 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 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 RCV001360460 SCV004847094 uncertain significance Retinoblastoma 2023-04-27 criteria provided, single submitter clinical testing This missense variant replaces threonine with alanine at codon 142 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 hereditary cancer in the literature. This variant has been identified in 1/31394 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 RCV004762120 SCV005372143 uncertain significance not provided 2023-07-27 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 23516486)

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