Submissions for variant NM_000546.5(TP53):c.613T>G (p.Tyr205Asp) (rs1057520008)

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000663307	SCV000786563	uncertain significance	Li-Fraumeni syndrome 1	2018-05-23	criteria provided, single submitter	clinical testing
Database of Curated Mutations (DoCM)	RCV000430021	SCV000510193	likely pathogenic	Ovarian Serous Cystadenocarcinoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000439865	SCV000510194	likely pathogenic	Squamous cell lung carcinoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000419128	SCV000510195	likely pathogenic	Pancreatic adenocarcinoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000428939	SCV000510196	likely pathogenic	Squamous cell carcinoma of the head and neck	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000439629	SCV000510197	likely pathogenic	Neoplasm of the large intestine	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000421350	SCV000510198	likely pathogenic	Multiple myeloma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000428535	SCV000510199	likely pathogenic	Neoplasm of the breast	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000438356	SCV000510200	likely pathogenic	Malignant neoplasm of body of uterus	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000421137	SCV000510201	likely pathogenic	Lung adenocarcinoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000434446	SCV000510202	likely pathogenic	Hepatocellular carcinoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000444873	SCV000510203	likely pathogenic	Glioblastoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000423676	SCV000510204	likely pathogenic	Non-Hodgkin lymphoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000434351	SCV000510205	likely pathogenic	Uterine Carcinosarcoma	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000444122	SCV000510206	likely pathogenic	Carcinoma of esophagus	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000426948	SCV000510207	likely pathogenic	Renal cell carcinoma, papillary, 1	2016-05-31	no assertion criteria provided	literature only
Database of Curated Mutations (DoCM)	RCV000436740	SCV000510208	likely pathogenic	Neoplasm of brain	2016-05-31	no assertion criteria provided	literature only
Invitae	RCV000462351	SCV000545314	uncertain significance	Li-Fraumeni syndrome	2016-07-05	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine with aspartic acid at codon 205 of the TP53 protein (p.Tyr205Asp). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in the germline of individuals with a TP53-related disease, but has been reported as a somatic variant in multiple tumor samples (PMID: 24009708, 17062677, 19064568, 23474753, 24091621). Experimental studies have shown that this variant disrupts TP53 transactivation activity in yeast-based assays (PMID: 12826609). In summary, this variant is a rare missense change that disrupts protein function in vitro. However, the evidence is insufficient at this time to prove its clinical significance conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.