ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.644G>A (p.Ser215Asn)

dbSNP: rs587782177
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 13
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492171 SCV000581094 likely pathogenic Hereditary cancer-predisposing syndrome 2013-01-08 criteria provided, single submitter clinical testing The p.S215N variant (also known as c.644G>A), located in coding exon 5 of the TP53 gene, results from a G to A substitution at nucleotide position 644. The serine at codon 215 is replaced by asparagine, an amino acid with highly similar properties. This alteration has been identified in a patient meeting Chompret criteria (Ambry internal data). Functional studies conducted in both yeast and mammalian cells indicate that this alteration is temperature sensitive, and is deficient at transactivation (IARC TP53 database; Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul;100:8424-9; Kakudo Y et al. Cancer Res., 2005 Mar;65:2108-14; Shiraishi K et al. J. Biol. Chem., 2004 Jan;279:348-55). In addition, studies conducted in human cell lines indicate that this alteration is deficient at growth suppression (Kotler E et al. Mol. Cell, 2018 Jul;71:178-190.e8). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD) (Lek M et al. Nature, 2016 08;536:285-91).This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Invitae RCV000816006 SCV000956491 uncertain significance Li-Fraumeni syndrome 2022-03-26 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 215 of the TP53 protein (p.Ser215Asn). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 376662). Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is expected to disrupt TP53 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.
Baylor Genetics RCV003476011 SCV004204250 likely pathogenic Adrenocortical carcinoma, hereditary 2023-04-14 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV004022241 SCV004931158 likely pathogenic Li-Fraumeni syndrome 1 2024-02-15 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 29979965]. This variant is expected to disrupt protein structure [Myriad internal data].
Database of Curated Mutations (DoCM) RCV000422423 SCV000509677 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427974 SCV000509678 likely pathogenic Ovarian serous cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438643 SCV000509679 likely pathogenic Small cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421424 SCV000509680 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432107 SCV000509681 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443221 SCV000509682 likely pathogenic Gastric adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423774 SCV000509683 likely pathogenic Acute myeloid leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434496 SCV000509684 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442434 SCV000509685 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.