ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.1053G>T (p.Lys351Asn)

dbSNP: rs1597349035
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001017149 SCV001178184 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-14 criteria provided, single submitter clinical testing The p.K351N variant (also known as c.1053G>T), located in coding exon 9 of the TP53 gene, results from a G to T substitution at nucleotide position 1053. The lysine at codon 351 is replaced by asparagine, an amino acid with similar properties. This variant is reported to have functional transactivation in yeast based assays (IARC TP53 database: Kato S et al. Proc. Natl. Acad. Sci. USA 2003 Jul;100:8424-9). Studies conducted in human cell lines indicate this alteration remains proficient at growth suppression (Kotler E et al. Mol.Cell, 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet., 2018 Oct;50:1381-1387). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction by BayesDel for this alteration is benign. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001220837 SCV001392849 uncertain significance Li-Fraumeni syndrome 2021-08-04 criteria provided, single submitter clinical testing 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on TP53 protein function (PMID: 12826609, 21953469). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 822085). This variant has not been reported in the literature in individuals affected with TP53-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with asparagine at codon 351 of the TP53 protein (p.Lys351Asn). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and asparagine.
Genome-Nilou Lab RCV002290534 SCV002582755 uncertain significance Li-Fraumeni syndrome 1 2022-06-18 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001017149 SCV002583217 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-18 criteria provided, single submitter clinical testing

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