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Catalog
2023 ACMG Annual Clinical Genetics Meeting Digital ...
Variant Overlooked: A Partial Deficiency
TP53< ...
Variant Overlooked: A Partial Deficiency
TP53
Allele that Skirts Interpretation Criteria
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Pdf Summary
Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by TP53 gene variants. The ClinGen TP53 Variant Curation Expert Panel (VCEP) recently published modified guidelines for TP53 variant interpretation. However, these guidelines do not fully account for a partial deficiency TP53 allele. <br /><br />In the case presented, a 17-year-old female with a family history of multiple cancers was diagnosed with grade 3 choroid plexus carcinoma. NGS sequencing identified a heterozygous missense change, c.589C>T p.(Val197Met), in TP53. However, according to the TP53 VCEP guidelines, this variant is classified as a variant of uncertain significance (VUS). <br /><br />The p.(Val197Met) variant is considered a partial deficiency allele and has been observed in patients with later-onset LFS spectrum cancers. The authors suggest that modifications to the TP53 VCEP guidelines are needed to accommodate these types of variants. They propose allowing for the incorporation of additional clinical information and/or less stringent metrics for evaluating partial deficiency alleles. <br /><br />In conclusion, the current TP53 VCEP scoring guidelines do not fully account for partial deficiency TP53 alleles like the p.(Val197Met) variant. The authors recommend modifications to the guidelines to improve the interpretation of these variants in the context of LFS.
Asset Subtitle
Co-Author - Lisa A. Lansdon; Co-Author - Florencia Del Viso, PhD; Co-Author - Caitlin Schwager, MS, CGC; Co-Author - Lei Zhang, PhD, FACMG; Co-Author - Sultan Habeebu, MD, PhD; Co-Author - Melissa Gener, MD; Co-Author - Midhat S. Farooqi, MD, PhD; Co-Author - Kevin Ginn, MD; Presenting Author - Joseph T. Alaimo, PhD, FACMG;
Meta Tag
array CGH
Cancer Syndromes
Genetic Testing
NextGen Sequencing
Pathology
Co-Author
Lisa A. Lansdon
Co-Author
Florencia Del Viso, PhD
Co-Author
Caitlin Schwager, MS, CGC
Co-Author
Lei Zhang, PhD, FACMG
Co-Author
Sultan Habeebu, MD, PhD
Co-Author
Melissa Gener, MD
Co-Author
Midhat S. Farooqi, MD, PhD
Co-Author
Kevin Ginn, MD
Presenting Author
Joseph T. Alaimo, PhD, FACMG
Keywords
Li-Fraumeni syndrome
LFS
TP53 gene variants
TP53 variant interpretation
partial deficiency TP53 allele
grade 3 choroid plexus carcinoma
heterozygous missense change
variant of uncertain significance
later-onset LFS spectrum cancers
modification to TP53 VCEP guidelines
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