ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.2774A>G (p.Lys925Arg)

gnomAD frequency: 0.00001  dbSNP: rs750946437
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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 RCV002034922 SCV002111056 uncertain significance Retinoblastoma 2023-02-14 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 925 of the RB1 protein (p.Lys925Arg). This variant is present in population databases (rs750946437, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with RB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1345099). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV003163999 SCV003913081 likely benign Hereditary cancer-predisposing syndrome 2023-03-02 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Baylor Genetics RCV004571125 SCV005054115 uncertain significance Malignant tumor of urinary bladder 2024-03-15 criteria provided, single submitter clinical testing

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