ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1245A>G (p.Ile415Met)

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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 RCV003514172 SCV004282469 uncertain significance Retinoblastoma 2023-08-07 criteria provided, single submitter clinical testing 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. 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) performed at Invitae indicates that this missense variant is not expected to disrupt RB1 protein function. This variant has not been reported in the literature in individuals affected with RB1-related conditions. This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 415 of the RB1 protein (p.Ile415Met).
Baylor Genetics RCV004574080 SCV005054151 uncertain significance Malignant tumor of urinary bladder 2023-12-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV004661685 SCV005160489 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-26 criteria provided, single submitter clinical testing The p.I415M variant (also known as c.1245A>G), located in coding exon 13 of the RB1 gene, results from an A to G substitution at nucleotide position 1245. The isoleucine at codon 415 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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