Total submissions: 20
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000709407 | SCV001429628 | likely pathogenic | Li-Fraumeni syndrome | 2020-08-11 | reviewed by expert panel | curation | 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 a BayesDel score > 0.16 and Align GVGD (Zebrafish) is Class 65 (PP3_Moderate). This variant has >10 observations as a somatic hotspot variant in tumors (PM1; cancerhotspots.org v(2)). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). In summary, TP53 c.396G>C (p.Lys132Asn) meets criteria to be classified as likely pathogenic for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: PS3, PP3_Moderate, PM1, PM2_Supporting. |
Mendelics | RCV000709407 | SCV000839122 | likely pathogenic | Li-Fraumeni syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000709407 | SCV000949001 | uncertain significance | Li-Fraumeni syndrome | 2019-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with asparagine at codon 132 of the TP53 protein (p.Lys132Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 376624). Experimental studies have shown that this missense change impairs the TP53 protein function (PMID: 12826609, 16861262). This variant disrupts the p.Lys132 amino acid residue in TP53. Other variants that disrupt this residue have been observed in affected individuals (PMID: 9157982, 18989156), which suggests that this may be a clinically significant amino acid residue. 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. |
Mendelics | RCV000424592 | SCV001140263 | likely pathogenic | Squamous cell carcinoma of the head and neck | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Database of Curated Mutations |
RCV000430184 | SCV000508716 | likely pathogenic | Uterine Carcinosarcoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000440843 | SCV000508717 | likely pathogenic | Adenocarcinoma of stomach | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000419339 | SCV000508718 | likely pathogenic | Lung adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000430063 | SCV000508719 | likely pathogenic | Squamous cell lung carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000439834 | SCV000508720 | likely pathogenic | Glioblastoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000422634 | SCV000508721 | likely pathogenic | Multiple myeloma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000432417 | SCV000508722 | likely pathogenic | Transitional cell carcinoma of the bladder | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000439586 | SCV000508723 | likely pathogenic | Carcinoma of esophagus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000421516 | SCV000508724 | likely pathogenic | Breast neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000432219 | SCV000508725 | likely pathogenic | Pancreatic adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000442734 | SCV000508726 | likely pathogenic | Neoplasm of uterine cervix | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000424592 | SCV000508727 | likely pathogenic | Squamous cell carcinoma of the head and neck | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000434424 | SCV000508728 | likely pathogenic | Ovarian Serous Cystadenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000442346 | SCV000508729 | likely pathogenic | Neoplasm of brain | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000427056 | SCV000508730 | likely pathogenic | Neoplasm of the large intestine | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000437720 | SCV000508731 | likely pathogenic | Adrenocortical carcinoma | 2016-05-31 | no assertion criteria provided | literature only |