Total submissions: 22
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV000991151 | SCV001142566 | pathogenic | Li-Fraumeni syndrome | 2019-08-28 | reviewed by expert panel | curation | This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has a BayesDel score > 0.16 and Align GVGD (Zebrafish) is Class 65 (PP3_Moderate). Transactivation assays show a low functioning allele according to Kato, et al. and there is evidence of a dominant negative effect and loss of function according to Giacomelli, et al. (PS3; PMID: 12826609, 30224644). This variant has been reported in at least 2 probands meeting Chompret criteria (PS4_Supporting; PMID: 28369373, 20308654). Additionally, there is one proband with a de novo observation of a Li-Fraumeni syndrome core cancer under the age of 5 years without parental confirmation (PM6; PMID: 25584008). In summary, the clinical significance of TP53 c.578A>C; p.His193Pro is pathogenic for Li-Fraumeni syndrome: PM2_Supporting, PP3_Moderate, PS3, PS4_Supporting, PM6. |
| Color Health, |
RCV001525967 | SCV001736190 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-06-22 | criteria provided, single submitter | clinical testing | This missense variant replaces histidine with proline at codon 193 of the TP53 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Experimental functional studies have shown that this variant disrupts TP53 transactivation activity, exhibits loss-of-function and dominant negative activity in human cell growth suppression assays, and results in loss-of-function in a human cell proliferation assay (PMID: (PMID: 22822097, 29979965, 30224644). This variant has been reported in 3 individuals meeting Chompret criteria affected with choroid plexus carcinoma and adrenocortical carcinoma (PMID: 20308654, 27501770), one of which was observed to occur de novo (PMID: 25584008), and another individual with soft tissue sarcoma and lung cancer (PMID: 28369373). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. |
| Database of Curated Mutations |
RCV000417520 | SCV000508526 | likely pathogenic | Neoplasm of the large intestine | 2016-05-31 | no assertion criteria provided | literature only | |
| Database of Curated Mutations |
RCV000428197 | SCV000508527 | likely pathogenic | Pancreatic adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
| Database of Curated Mutations |
RCV000435420 | SCV000508528 | likely pathogenic | Chronic lymphocytic leukemia | 2016-05-31 | no assertion criteria provided | literature only | |
| Database of Curated Mutations |
RCV000418213 | SCV000508529 | likely pathogenic | Adenocarcinoma of prostate | 2016-05-31 | no assertion criteria provided | literature only | |
| Database of Curated Mutations |
RCV000428877 | SCV000508530 | likely pathogenic | Brainstem glioma | 2016-05-31 | no assertion criteria provided | literature only | |
| Database of Curated Mutations |
RCV000439568 | SCV000508531 | likely pathogenic | Uterine Carcinosarcoma | 2016-05-31 | no assertion criteria provided | literature only | |
| Database of Curated Mutations |
RCV000422374 | SCV000508532 | likely pathogenic | Carcinoma of esophagus | 2016-05-31 | no assertion criteria provided | literature only | |
| Database of Curated Mutations |
RCV000429577 | SCV000508533 | likely pathogenic | Adenocarcinoma of stomach | 2016-05-31 | no assertion criteria provided | literature only | |
| Database of Curated Mutations |
RCV000440128 | SCV000508534 | likely pathogenic | Breast neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
| Database of Curated Mutations |
RCV000422912 | SCV000508535 | likely pathogenic | Small cell lung carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
| Database of Curated Mutations |
RCV000433585 | SCV000508536 | likely pathogenic | Lung adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
| Database of Curated Mutations |
RCV000442541 | SCV000508537 | likely pathogenic | Malignant neoplasm of body of uterus | 2016-05-31 | no assertion criteria provided | literature only | |
| Database of Curated Mutations |
RCV000423516 | SCV000508538 | likely pathogenic | Squamous cell lung carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
| Database of Curated Mutations |
RCV000434205 | SCV000508539 | likely pathogenic | Transitional cell carcinoma of the bladder | 2016-05-31 | no assertion criteria provided | literature only | |
| Database of Curated Mutations |
RCV000445292 | SCV000508540 | likely pathogenic | Ovarian Serous Cystadenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
| Database of Curated Mutations |
RCV000427668 | SCV000508541 | likely pathogenic | Acute myeloid leukemia | 2016-05-31 | no assertion criteria provided | literature only | |
| Database of Curated Mutations |
RCV000434933 | SCV000508542 | likely pathogenic | Squamous cell carcinoma of the head and neck | 2016-05-31 | no assertion criteria provided | literature only | |
| Database of Curated Mutations |
RCV000444985 | SCV000508543 | likely pathogenic | Hepatocellular carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
| Database of Curated Mutations |
RCV000424851 | SCV000508544 | likely pathogenic | Papillary renal cell carcinoma, sporadic | 2016-05-31 | no assertion criteria provided | literature only | |
| Database of Curated Mutations |
RCV000435566 | SCV000508545 | likely pathogenic | Neoplasm of brain | 2016-05-31 | no assertion criteria provided | literature only |