ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1468G>T (p.Ala490Ser)

dbSNP: rs201458896
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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 RCV001210843 SCV001382351 uncertain significance Retinoblastoma 2023-02-28 criteria provided, single submitter clinical testing 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) performed at Invitae indicates that this missense variant is not expected to disrupt RB1 protein function. This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 490 of the RB1 protein (p.Ala490Ser). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with clinical features of RB1-related conditions (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 941124). 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 RCV002393480 SCV002698830 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-13 criteria provided, single submitter clinical testing The p.A490S variant (also known as c.1468G>T), located in coding exon 16 of the RB1 gene, results from a G to T substitution at nucleotide position 1468. The alanine at codon 490 is replaced by serine, an amino acid with similar properties. This amino acid position is highly 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 RCV001210843 SCV004814340 uncertain significance Retinoblastoma 2023-08-15 criteria provided, single submitter clinical testing

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