ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.695T>A (p.Ile232Asn)

dbSNP: rs587781589
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetics and Molecular Pathology, SA Pathology RCV001054089 SCV002761668 likely pathogenic Li-Fraumeni syndrome 2021-08-23 criteria provided, single submitter clinical testing The TP53 c.695T>A variant is classified as Likely Pathogenic (PS3, PM2, PP3) This variant is absent from population databases (PM2). Well-established functional studies show a deleterious effect of this variant ( IARC TP53 database indicates the variant results in a non-functional protein with respect to transactivation of downstream genes using the assay of (Kato et al., 2003 PMID: 12826609) ) (PS3). Variant occurs in the DNA binding domain, and demonstrates growth suppression. Computational predictions support a deleterious effect on the gene or gene product (PP3).
Labcorp Genetics (formerly Invitae), Labcorp RCV001054089 SCV001218384 pathogenic Li-Fraumeni syndrome 2025-06-02 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 232 of the TP53 protein (p.Ile232Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Li-Fraumeni syndrome (LFS) (internal data). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 850008). Invitae Evidence Modeling incorporating data from in vitro 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%. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609). For these reasons, this variant has been classified as Pathogenic.
Department of Clinical Biochemistry, Naestved Hospital RCV006250181 SCV006076889 tier ii - potential Colorectal cancer 2024-10-10 no assertion criteria provided research Missense. Likely loss of function.

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