Total submissions: 10
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Dasa | RCV000236210 | SCV007599480 | pathogenic | not provided | 2024-06-13 | criteria provided, single submitter | clinical testing | NM_000546.6(TP53):c.722C>G (p.Ser241Cys) is a missense variant that results in the substitution of serine with cysteine. The affected residue or protein region has prior evidence supporting clinical relevance. This variant has been reported in individuals with related phenotype. Functional evidence supports a deleterious effect on the gene or gene product. The variant is present at low frequency in population datasets. Based on the available data, this variant is classified as pathogenic. |
| Center for Genomic Medicine, |
RCV006273569 | SCV007129856 | likely oncogenic | Neoplasm | 2025-12-29 | criteria provided, single submitter | clinical testing | |
| Myriad Genetics, |
RCV002288664 | SCV004932198 | likely pathogenic | Li-Fraumeni syndrome 1 | 2024-02-16 | 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]. |
| Labcorp Genetics |
RCV000154419 | SCV003253335 | likely pathogenic | Li-Fraumeni syndrome | 2024-06-09 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 241 of the TP53 protein (p.Ser241Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Li-Fraumeni syndrome and/or ovarian cancer (PMID: 30730202, 35451682). ClinVar contains an entry for this variant (Variation ID: 177791). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is expected to disrupt TP53 function with a positive predictive value of 97.5%. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 29979965, 30224644). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Genome- |
RCV002288664 | SCV002583024 | likely pathogenic | Li-Fraumeni syndrome 1 | 2022-06-18 | criteria provided, single submitter | clinical testing | |
| Genome- |
RCV000492778 | SCV002582363 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-06-18 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000492778 | SCV000581139 | pathogenic | Hereditary cancer-predisposing syndrome | 2025-05-23 | criteria provided, single submitter | clinical testing | The p.S241C pathogenic mutation (also known as c.722C>G), located in coding exon 6 of the TP53 gene, results from a C to G substitution at nucleotide position 722. The serine at codon 241 is replaced by cysteine, an amino acid with dissimilar properties. This variant is in the DNA binding domain of the TP53 protein and is reported to have non-functional transactivation in yeast-based assays (Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul;100:8424-9). Studies conducted in human cell lines indicate this alteration is deficient at growth suppression and has a dominant negative effect (Kotler E et al. Mol.Cell. 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This mutation has been identified in a family meeting classic Li-Fraumeni syndrome criteria (Sejben A et al. Orv Hetil 2019 Feb;160(6):228-234). This alteration has been observed numerous times as a somatic mutation in the cancerhotspots.org database (Chang MT et al. Cancer Discov. 2018 02;8:174-183). This variant was detected in at least one individual at an allele fraction that is suggestive of clonal hematopoiesis, a predictor of TP53 pathogenicity (Ambry internal data; Fortuno C et al. Genet Med. 2022 03;24:673-680). This amino acid position is highly conserved in available vertebrate species. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Gene |
RCV000236210 | SCV000293500 | pathogenic | not provided | 2024-01-05 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect: non-functional transactivation and impaired growth suppression activity (PMID: 12826609, 29979965, 30224644, 20407015); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 20407015, 16312222, 24997986, 11301359, 23168708, 12144684, 15564288, 2024123, 8934544, 11079169, 11389059, 15064998, 16174251, 10690522, 21552959, 10951339, 15837541, 9792155, 25839328, 23349305, 15915369, 20404136, 19509155, 25356985, 28803919, 28861920, 30840781, 30224644, 29979965, 26619011, 34273903, 15510160, 35451682, 12826609, 30730202) |
| German Consortium for Hereditary Breast and Ovarian Cancer, |
RCV000785321 | SCV000923889 | likely pathogenic | Ovarian neoplasm | 2018-12-01 | no assertion criteria provided | research | |
| Laboratory for Molecular Medicine, |
RCV000154419 | SCV000204087 | likely pathogenic | Li-Fraumeni syndrome | 2008-01-03 | no assertion criteria provided | clinical testing |