ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.1120G>A (p.Gly374Ser) (rs587781858)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130166 SCV000185002 uncertain significance Hereditary cancer-predisposing syndrome 2016-01-12 criteria provided, single submitter clinical testing The p.G374S variant (also known as c.1120G>A), located in coding exon 10 of the TP53 gene, results from a G to A substitution at nucleotide position 1120. The glycine at codon 374 is replaced by serine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 200000 alleles tested) in our clinical cohort. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of p.G374S remains unclear.
Color Health, Inc RCV000130166 SCV000906812 likely benign Hereditary cancer-predisposing syndrome 2016-10-07 criteria provided, single submitter clinical testing
Invitae RCV001313040 SCV001503515 uncertain significance Li-Fraumeni syndrome 2020-09-15 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 374 of the TP53 protein (p.Gly374Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 141583). This variant has been reported not to substantially affect TP53 protein function (PMID: 12826609, 30224644). 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.

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