Submissions for variant NM_000546.6(TP53):c.782+1G>A

dbSNP: rs1555525429

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001063778	SCV001228639	pathogenic	Li-Fraumeni syndrome	2024-10-23	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 7 of the TP53 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with breast cancer (PMID: 29070607). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 634684). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne	RCV000785278	SCV000923846	likely pathogenic	Ovarian neoplasm	2018-12-01	no assertion criteria provided	research
MutSpliceDB: a database of splice sites variants effects on splicing, NIH	RCV001528108	SCV001739279	not provided	not provided		no assertion provided	in vivo