Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001068360 | SCV001233467 | uncertain significance | Li-Fraumeni syndrome | 2019-03-25 | 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. An experimental study in yeast has shown that this variant does not impair the transcriptional transactivation activity of the TP53 protein (PMID: 12826609). This variant has not been reported in the literature in individuals with TP53-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glutamine at codon 3 of the TP53 protein (p.Glu3Gln). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and glutamine. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002282452 | SCV002571868 | uncertain significance | not specified | 2022-08-08 | criteria provided, single submitter | clinical testing | Variant summary: TP53 c.7G>C (p.Glu3Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 250540 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.7G>C in individuals affected with Li-Fraumeni Syndrome has been reported. Experimental evidence using yeast-based functional assays showed that the variant had no damaging effect on protein function (Kato_2003, PHANTM database). One ClinVar submitter has assessed the variant since 2014: the variant was classified as of uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Liquid Biopsy and Cancer Interception Group, |
RCV003128747 | SCV003806394 | uncertain significance | Lung adenocarcinoma | 2022-06-06 | criteria provided, single submitter | research |