ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.104A>T (p.Gln35Leu)

gnomAD frequency: 0.00001  dbSNP: rs1480581747
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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 RCV000699680 SCV000828403 uncertain significance Retinoblastoma 2022-11-29 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RB1 protein function. ClinVar contains an entry for this variant (Variation ID: 577029). 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 glutamine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 35 of the RB1 protein (p.Gln35Leu).
Ambry Genetics RCV001017125 SCV001178157 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-09 criteria provided, single submitter clinical testing The p.Q35L variant (also known as c.104A>T), located in coding exon 1 of the RB1 gene, results from an A to T substitution at nucleotide position 104. The glutamine at codon 35 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate 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.
All of Us Research Program, National Institutes of Health RCV000699680 SCV004846308 uncertain significance Retinoblastoma 2023-09-17 criteria provided, single submitter clinical testing This missense variant replaces glutamine with leucine at codon 35 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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