Total submissions: 13
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, |
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 |
RCV000422423 | SCV000509677 | likely pathogenic | Hepatocellular carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000427974 | SCV000509678 | likely pathogenic | Ovarian serous cystadenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000438643 | SCV000509679 | likely pathogenic | Small cell lung carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000421424 | SCV000509680 | likely pathogenic | Pancreatic adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000432107 | SCV000509681 | likely pathogenic | Carcinoma of esophagus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000443221 | SCV000509682 | likely pathogenic | Gastric adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000423774 | SCV000509683 | likely pathogenic | Acute myeloid leukemia | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000434496 | SCV000509684 | likely pathogenic | Breast neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000442434 | SCV000509685 | likely pathogenic | Lung adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only |