ClinVar Miner

Submissions for variant NM_000321.2(RB1):c.34A>G (p.Thr12Ala)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000822727 SCV000963542 uncertain significance Retinoblastoma 2018-10-23 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 12 of the RB1 protein (p.Thr12Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals with RB1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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