Submissions for variant NM_000546.6(TP53):c.993+1G>T

dbSNP: rs11575997

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001062298	SCV001227088	pathogenic	Li-Fraumeni syndrome	2022-08-09	criteria provided, single submitter	clinical testing	Disruption of this splice site has been observed in individual(s) with Li-Fraumeni syndrome (PMID: 10980596). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 634766). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 9 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).
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne	RCV000785504	SCV000924076	likely pathogenic	Ovarian neoplasm	2018-12-01	no assertion criteria provided	research
MutSpliceDB: a database of splice sites variants effects on splicing, NIH	RCV000786815	SCV000925707	not provided	not provided		no assertion provided	in vitro
Key Laboratory of Carcinogenesis and Cancer Invasion, Central South University	RCV004001541	SCV004046834	likely pathogenic	Adrenal cortex carcinoma		no assertion criteria provided	clinical testing