ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.700T>G (p.Tyr234Asp)

dbSNP: rs864622237
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Total submissions: 17
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000204217 SCV000259812 pathogenic Li-Fraumeni syndrome 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 234 of the TP53 protein (p.Tyr234Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with chronic lymphocytic leukemia and/or clinical features of Li-Fraumeni syndrome (PMID: 21232794; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 219759). 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%. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000492197 SCV000581114 pathogenic Hereditary cancer-predisposing syndrome 2021-02-04 criteria provided, single submitter clinical testing The p.Y234D pathogenic mutation (also known as c.700T>G), located in coding exon 6 of the TP53 gene, results from a T to G substitution at nucleotide position 700. The tyrosine at codon 234 is replaced by aspartic acid, an amino acid with highly dissimilar properties. This variant has been detected in individuals meeting clinical criteria for classic Li-Fraumeni syndrome (Ambry internal data). 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). In addition, this alteration is predicted to be deleterious by in silico analysis. Two other alterations at the same codon, p.Y234H and p.Y234S, have been reported in families with Li-Fraumeni syndrome (Mitchell G et al. PLoS ONE 2013 ; 8(7):e69026; Ambry internal data). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc. RCV004020511 SCV004931622 likely pathogenic Li-Fraumeni syndrome 1 2024-02-15 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].
Database of Curated Mutations (DoCM) RCV000418073 SCV000510341 likely pathogenic Prostate adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430896 SCV000510342 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441597 SCV000510343 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424345 SCV000510344 likely pathogenic Gastric adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433328 SCV000510345 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440475 SCV000510346 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423238 SCV000510347 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433956 SCV000510348 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000445176 SCV000510349 likely pathogenic Ovarian serous cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425587 SCV000510350 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432845 SCV000510351 likely pathogenic Small cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000445265 SCV000510352 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424462 SCV000510353 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435222 SCV000510354 likely pathogenic Adrenal cortex carcinoma 2016-05-31 no assertion criteria provided literature only

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