ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.706T>A (p.Tyr236Asn)

dbSNP: rs587782289
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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000463978 SCV000545294 uncertain significance Li-Fraumeni syndrome 2020-02-05 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 376694). 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. This variant has been reported not to substantially affect TP53 protein function (PMID: 12826609, 15580553). This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with asparagine at codon 236 of the TP53 protein (p.Tyr236Asn). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and asparagine.
Ambry Genetics RCV000566931 SCV000672389 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-20 criteria provided, single submitter clinical testing The p.Y236N variant (also known as c.706T>A), located in coding exon 6 of the TP53 gene, results from a T to A substitution at nucleotide position 706. The tyrosine at codon 236 is replaced by asparagine, an amino acid with dissimilar properties. This variant is in the DNA binding domain of the TP53 protein and is reported to have functional transactivation in yeast based assays (Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul;100:8424-9). However, 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). This alteration has been detected in a proband meeting Chompret criteria for Li-Fraumeni syndrome (LFS) (Ambry internal data). In addition, other alterations at this codon (p.Y236H, p.Y236C, p.Y236D) have been detected in individuals with Li-Fraumeni syndrome (Rines R et al. Carcinogenesis. 1998 Jun;19(6):979-84; Ambry Internal data). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is conflicting at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV000566931 SCV002582016 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-18 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002289545 SCV002582113 uncertain significance Li-Fraumeni syndrome 1 2022-06-18 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV002289545 SCV004931605 likely pathogenic Li-Fraumeni syndrome 1 2024-02-16 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) RCV000439518 SCV000510366 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422301 SCV000510367 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432981 SCV000510368 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444573 SCV000510369 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421176 SCV000510370 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431852 SCV000510371 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444665 SCV000510372 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427088 SCV000510373 likely pathogenic Ovarian serous cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438025 SCV000510374 likely pathogenic Prostate adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443891 SCV000510375 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426248 SCV000510376 likely pathogenic Gastric adenocarcinoma 2016-05-31 no assertion criteria provided literature only

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