ClinVar Miner

Submissions for variant NM_001126112.2(TP53):c.839G>C (p.Arg280Thr) (rs121912660)

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Total submissions: 19
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000198779 SCV000254639 uncertain significance Li-Fraumeni syndrome 2017-02-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with threonine at codon 280 of the TP53 protein (p.Arg280Thr). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and threonine. This variant is not present in population databases (rs121912660, ExAC no frequency). This variant has been reported in an individual affected with breast cancer (PMID: 25927356). ClinVar contains an entry for this variant (Variation ID: 12368). Experimental studies have shown that this missense change disrupts the function of TP53 (PMID: 22999923, 12826609). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated and algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but these predictions have not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in an affected individual, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
OMIM RCV000013167 SCV000033414 pathogenic Nasopharyngeal carcinoma 1992-07-15 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424688 SCV000509523 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434981 SCV000509524 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418209 SCV000509525 likely pathogenic Small cell lung cancer 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428404 SCV000509526 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437764 SCV000509527 likely pathogenic Nasopharyngeal Neoplasms 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420086 SCV000509528 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431210 SCV000509529 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441513 SCV000509530 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422958 SCV000509531 likely pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429718 SCV000509532 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440816 SCV000509533 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423074 SCV000509534 likely pathogenic Acute myeloid leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432461 SCV000509535 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441912 SCV000509536 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422446 SCV000509537 likely pathogenic Uterine cervical neoplasms 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432716 SCV000509538 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000445307 SCV000509539 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only

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