Submissions for variant NM_000546.6(TP53):c.359A>T (p.Lys120Met)

dbSNP: rs2073450819

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001174845	SCV001338227	uncertain significance	not specified	2020-08-28	criteria provided, single submitter	clinical testing	Variant summary: TP53 c.359A>T (p.Lys120Met) results in a non-conservative amino acid change located in the DNA-binding domain (IPR010991) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251048 control chromosomes. To our knowledge, there are no reports of c.359A>T in individuals affected with Li-Fraumeni Syndrome. However, somatic occurrences of this variant have been reported in individuals affected with various cancer phenotypes (Examples- Zenz_2010, Dumont_2014, Malcikova_2015, Nikbakht_2016). At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in 10%-<30% of normal transcriptional activity in a yeast-based assay (Kato_2003). No other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.