Submissions for variant NM_000546.6(TP53):c.613T>G (p.Tyr205Asp)

dbSNP: rs1057520008

Total submissions: 20

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000462351	SCV000545314	pathogenic	Li-Fraumeni syndrome	2023-08-19	criteria provided, single submitter	clinical testing	This variant disrupts the p.Tyr205 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10922393, 12826609, 16861262, 17724467, 20505364, 21356188, 29324801, 29979965, 30224644). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 29979965, 30224644). 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. ClinVar contains an entry for this variant (Variation ID: 376686). This missense change has been observed in individual(s) with sarcoma (PMID: 29070607). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 205 of the TP53 protein (p.Tyr205Asp).
Counsyl	RCV000663307	SCV000786563	uncertain significance	Li-Fraumeni syndrome 1	2018-05-23	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000663307	SCV004017828	likely pathogenic	Li-Fraumeni syndrome 1	2023-04-11	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].
GeneDx	RCV003441853	SCV004168968	pathogenic	not provided	2023-04-05	criteria provided, single submitter	clinical testing	Published functional studies demonstrate a damaging effect: non-functional transactivation, loss of growth suppression ability (Kato et al., 2003; Giacomelli et al., 2018; Kotler et al., 2018); 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: 15510160, 20505364, 17724467, 16861262, 12826609, 26619011, 30224644, 29979965, 29070607, 10922393, 29324801, 21356188, 30840781)
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	Breast neoplasm	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	Papillary renal cell carcinoma type 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