Submissions for variant NM_000546.6(TP53):c.672+6_672+8delinsTTG

dbSNP: rs2073318029

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001192010	SCV001359953	uncertain significance	Hereditary cancer-predisposing syndrome	2021-10-25	criteria provided, single submitter	clinical testing	This variant causes a substitution of three nucleotides in intron 6 of the TP53 gene (c.672+6_672+8delinsTTG). Splice prediction tools suggest this variant may not affect RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001799046	SCV002042831	uncertain significance	Breast and/or ovarian cancer	2022-05-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001192010	SCV002582027	uncertain significance	Hereditary cancer-predisposing syndrome	2022-06-18	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002290628	SCV002582224	uncertain significance	Li-Fraumeni syndrome 1	2022-06-18	criteria provided, single submitter	clinical testing
Invitae	RCV003621587	SCV004474650	uncertain significance	Li-Fraumeni syndrome	2019-06-04	criteria provided, single submitter	clinical testing	This sequence change falls in intron 6 of the TP53 gene. It does not directly change the encoded amino acid sequence of the TP53 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs766856111, ExAC 0.002%). This variant has not been reported in the literature in individuals with TP53-related conditions. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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.