ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.751A>C (p.Ile251Leu) (rs730882007)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000161037 SCV000211759 pathogenic not provided 2016-05-27 criteria provided, single submitter clinical testing The I251L (ATC>CTC) missense variant in the TP53 gene, denoted c.751A>C at the cDNA level, has been reported previously in association with Li-Fraumeni syndrome (Wu et al., 2011). Additionally, the NHLBI ESP Exome Variant Server reports I251L was not observed in approximately 6,500 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. Therefore, I251L is interpreted as a disease-causing variant.
Ambry Genetics RCV000492548 SCV000581167 likely pathogenic Hereditary cancer-predisposing syndrome 2016-12-08 criteria provided, single submitter clinical testing The p.I251L variant (also known as c.751A>C), located in coding exon 6 of the TP53 gene, results from an A to C substitution at nucleotide position 751. The isoleucine at codon 251 is replaced by leucine, an amino acid with highly similar properties. This alteration has been reported in the literature in one family with Li-Fraumeni syndrome (Wu CC et al. Hum. Genet. 2011 Jun; 129(6):663-73). This alteration is in the DNA binding domain of the TP53 protein and is reported to have loss of transactivation capacity (Kato S et al. Proc Natl Acad Sci USA. 2003 Jul 8;100(14):8424-9). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital RCV000161037 SCV001449920 likely pathogenic not provided 2018-06-25 criteria provided, single submitter clinical testing
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785277 SCV000923845 likely pathogenic Neoplasm of ovary 2018-12-01 no assertion criteria provided research

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