ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.585C>G (p.Ile195Met) (rs1057519994)

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Total submissions: 17
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Database of Curated Mutations (DoCM) RCV000419550 SCV000508672 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429834 SCV000508673 likely pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436566 SCV000508674 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418858 SCV000508675 likely pathogenic Acute myeloid leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429158 SCV000508676 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439382 SCV000508677 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421371 SCV000508678 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428127 SCV000508679 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438380 SCV000508680 likely pathogenic Chronic lymphocytic leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424140 SCV000508681 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434462 SCV000508682 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442092 SCV000508683 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423525 SCV000508684 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433822 SCV000508685 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442140 SCV000508686 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426409 SCV000508687 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Invitae RCV000633400 SCV000754622 uncertain significance Li-Fraumeni syndrome 2017-10-30 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with methionine at codon 195 of the TP53 protein (p.Ile195Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 376620). Experimental studies have shown that this missense change partially disrupts the ability of p53 to bind to DNA and consequently to transactivate downstream genes (PMID: 12826609). A different missense substitution at this codon (p.Ile195Thr) has been determined to be pathogenic (PMID: 27501770, 19405127). This suggests that the isoleucine residue is critical for TP53 protein function and that other missense substitutions at this position may also be pathogenic. 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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