ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.644G>T (p.Ser215Ile) (rs587782177)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001025280 SCV001187441 pathogenic Hereditary cancer-predisposing syndrome 2019-12-05 criteria provided, single submitter clinical testing The p.S215I pathogenic mutation (also known as c.644G>T), located in coding exon 5 of the TP53 gene, results from a G to T substitution at nucleotide position 644. The serine at codon 215 is replaced by isoleucine, an amino acid with dissimilar properties. This variant is in the DNA binding domain of the TP53 protein and is reported to have loss of transactivation in yeast based assays (IARC TP53 database: Kato S et al. Proc. Natl. Acad. Sci. USA 2003 Jul;100:8424-9). Additional studies conducted in human cell lines indicate this alteration has a dominant negative effect and is deficient at growth suppression (Kotler E et al. Mol. Cell. 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). Based on internal structural assessment, this alteration destabilized the DNA-binding domain (Cho Y et al. Science. 1994 Jul;265:346-55; Ambry internal data). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Database of Curated Mutations (DoCM) RCV000435696 SCV000509650 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420217 SCV000509651 likely pathogenic Small cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430889 SCV000509652 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441630 SCV000509653 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420881 SCV000509654 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429840 SCV000509655 likely pathogenic Acute myeloid leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440493 SCV000509656 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423272 SCV000509657 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433950 SCV000509658 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785347 SCV000923915 likely pathogenic Neoplasm of ovary 2018-12-01 no assertion criteria provided research

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